Naunyn-schmiedebergs Archives of Pharmacology, 1996
The messenger RNA (mRNA) expression of somatostatin receptors sst1–5 was studied in human brain b... more The messenger RNA (mRNA) expression of somatostatin receptors sst1–5 was studied in human brain by in situ hybridization histochemistry using specific oligonucleotide probes. sst1 receptor mRNA was mainly found in the outer and intermediate layers of cerebral cortex, hippocampal formation (CA1, dentate gyrus, entorhinal cortex), hypothalamus, substantia nigra, medullary nuclei and dentate nucleus. sst2 transcripts were present in the deep layers of the cerebral cortex, amygdala, hippocampal formation (CA1, dentate gyrus, subiculum, entorhinal cortex), the granular layer of the cerebellum and pituitary. sst3 receptor mRNA was localized in the cerebral cortex, hippocampal formation (CA1, dentate gyrus), several medullary nuclei and the granule and possibly Purkinje cell layer of the cerebellum and at very low levels in the pituitary. sst4 receptor mRNA was absent in the cerebral cortex. Intermediate signals were observed in the dentate gyrus of the hippocampus and several medullary nuclei while an intense expression was found in the granule and Purkinje cell layer of cerebellum. sst5 transcripts were present in the pituitary and the granule layer of the cerebellum. The present results show that mRNAs of sst1–4 somatostatin receptors have distinct distribution patterns within the human brain, although there is overlap in several regions. sst5 receptor mRNA expression appears to be very low and restricted to the cerebellum and pituitary. The distribution pattern observed in the human brain was broadly similar to that reported previously in the rat brain. The high expression levels of at least two somatostatin receptor subtype mRNAs (sst2 and sst5) in the pituitary gland suggest that somatostatin may affect neuroendocrine functions via more than one receptor.
Somatostatin regulates endocrine and exocrine secretion, acts as a neurotransmitter/neuro-modulat... more Somatostatin regulates endocrine and exocrine secretion, acts as a neurotransmitter/neuro-modulator and possesses antiproliferative properties. These diverse physiological effects are mediated by G-protein coupled receptors of which at least five subtypes have been cloned (SSTR1-5). Here, we have investigated the tissue distribution pattern of mRNAs encoding the five SRIF receptor subtypes in the adult rat by RT-PCR analysis and in situ hybridization histochemistry. All five receptor subtypes were found to be expressed simultaneously in brain and pituitary by RT-PCR. Besides, the in situ hybridization results clearly show a distinct but overlapping expression pattern of SSTR1-5 mRNA in the central nervous system as was found by RT-PCR for the periphery. Such distinct SRIF receptor expression may contribute to the selective biological functions of the receptor subtypes.
European Journal of Pharmacology: Molecular Pharmacology, 1995
Somatostatin (SRIF) SS-1 binding sites were initially defined in radioligand binding studies perf... more Somatostatin (SRIF) SS-1 binding sites were initially defined in radioligand binding studies performed in rat brain cerebral cortex membranes using [125I]204-090 (a radiolabelled Tyr 3 analogue of SMS 201-995, octreotide). SRIF-1 recognition sites were defincd in binding studies performed with [125I]MK 678 (scglitide). Both SS-I and SRIF-1 sites were characterized by their high affinity for SRIF-14, SRIF-28 and for cyclic peptidcs such as octreotide and seglitide, in marked contrast to SSo2 and SRIF-2 sites which have very low affinity for these synthetic SRIF analogues. In the present study, SS-1 and SRIF-1 radioligand binding studies were performed in rat cortex membranes and compared to results obtained in cloned Chinese hamster ovary cells expressing human SSTR-2 receptors using [125I]204-090 and/or [125I]MK-678. The rank orders of affinity of a variety of SRIF analogues and synthetic pcptides for SS-1/SRIF-I binding sites and recombinant SSTR-2 receptors were very similar and correlated highly significantly (r = 0.94-0.99); by contrast, correlation between SS-1 and SSTR-5 (r = 0.44) or SSTR-3 binding (r = 0.07) was not significant. Autoradiographic studies were performed in rat brain using both radioligands [125I]204-090 and [1251]MK-678 and compared with the distribution of SSTR-2 receptor mRNA determined using in situ hybridization. A clear overlap was observed between the distribution of SSTR-2 mRNA and binding sites labelled with both radioligands. SSTR-2 receptor-mediated inhibition of forskolin-stimulated adenylate cyclase in Chines hamster ovary cells by a variety of SRIF analogues and short synthetic peptides displayed a rank order of potency highly similar to their rank order of affinity at SS-1/SRIF-I binding sites. It is concluded that SS-I and SRIF-1 binding sites respectively labelled with [125I]204-090 and [~25I]MK 678, both display the pharmacological profile of SSTR-2 receptors, that the distribution of [12511204-090 and [1251]MK-678 binding sites in rat brain is superimposable and largely comparable to that of SSTR-2 mRNA expression. It is also shown that neither [125I]204-090 nor [125I]MK-678 label SSTR-3 or SSTR-5 receptors in rat brain. Finally, it is demonstrated that SSTR-2 receptors can very efficiently couple to adenylate cyclase activity in an inhibitory manner.
Naunyn-schmiedebergs Archives of Pharmacology, 1994
In situ hybridization histochemistry was performed to analyse the distribution of the messenger R... more In situ hybridization histochemistry was performed to analyse the distribution of the messenger RNA (mRNA) of three putative somatostatin (SRIF) receptors in rat brain, using oligonucleotide probes derived from the cDNA coding for SSTR-1, SSTR-2, and SSTR-3 receptors. SSTR-1 signals were found in layers VVI of the cerebral cortex, in primary olfactory cortex, taenia tecta, subiculum, entorhinal cortex, granular layer of the dentate gyrus, amygdala and cerebellar nuclei. Signals for SSTR-2 were found in the frontal cerebral cortex (layers IV, V and VI), taenia tecta, claustrum, endopiriform nucleus, locus coeruleus, medial habenula, subiculum, granular cell layer of the dentate gyrus and amygdala. High levels of SSTR-3 hybridization were found in the olfactory bulb, primary olfactory cortex, islands of Calleja, medial habenula, amygdala, granular layer of the dentate gyrus, various thalamic and pontine nuclei and in the granular and Purkinje cell layers of the cerebellum. The distribution of the hybridization signals of the oligoprobes is consistent with the labelling of specific SRIF binding sites in rat brain. Especially, SSTR-2 and SSTR-1 oligos seem to label regions in which SS-1 and SS-2 receptors, respectively, have been previously characterized in autoradiographical studies. The situation is less clear with SSTR-3 mRNA, since SRIF binding in adult rats is usually low or absent in cerebellum, although some cerebellar nuclei appear to be labelled in the adult. The localization of SSTR-1, SSTR-2 and SSTR-3 mRNAs suggests that SRIF receptor subtypes in rat brain show profound differences in their distribution and are involved in a variety of central, in addition to neuroendocrine, functions.
Naunyn-schmiedebergs Archives of Pharmacology, 1996
The messenger RNA (mRNA) expression of somatostatin receptors sst1–5 was studied in human brain b... more The messenger RNA (mRNA) expression of somatostatin receptors sst1–5 was studied in human brain by in situ hybridization histochemistry using specific oligonucleotide probes. sst1 receptor mRNA was mainly found in the outer and intermediate layers of cerebral cortex, hippocampal formation (CA1, dentate gyrus, entorhinal cortex), hypothalamus, substantia nigra, medullary nuclei and dentate nucleus. sst2 transcripts were present in the deep layers of the cerebral cortex, amygdala, hippocampal formation (CA1, dentate gyrus, subiculum, entorhinal cortex), the granular layer of the cerebellum and pituitary. sst3 receptor mRNA was localized in the cerebral cortex, hippocampal formation (CA1, dentate gyrus), several medullary nuclei and the granule and possibly Purkinje cell layer of the cerebellum and at very low levels in the pituitary. sst4 receptor mRNA was absent in the cerebral cortex. Intermediate signals were observed in the dentate gyrus of the hippocampus and several medullary nuclei while an intense expression was found in the granule and Purkinje cell layer of cerebellum. sst5 transcripts were present in the pituitary and the granule layer of the cerebellum. The present results show that mRNAs of sst1–4 somatostatin receptors have distinct distribution patterns within the human brain, although there is overlap in several regions. sst5 receptor mRNA expression appears to be very low and restricted to the cerebellum and pituitary. The distribution pattern observed in the human brain was broadly similar to that reported previously in the rat brain. The high expression levels of at least two somatostatin receptor subtype mRNAs (sst2 and sst5) in the pituitary gland suggest that somatostatin may affect neuroendocrine functions via more than one receptor.
Somatostatin regulates endocrine and exocrine secretion, acts as a neurotransmitter/neuro-modulat... more Somatostatin regulates endocrine and exocrine secretion, acts as a neurotransmitter/neuro-modulator and possesses antiproliferative properties. These diverse physiological effects are mediated by G-protein coupled receptors of which at least five subtypes have been cloned (SSTR1-5). Here, we have investigated the tissue distribution pattern of mRNAs encoding the five SRIF receptor subtypes in the adult rat by RT-PCR analysis and in situ hybridization histochemistry. All five receptor subtypes were found to be expressed simultaneously in brain and pituitary by RT-PCR. Besides, the in situ hybridization results clearly show a distinct but overlapping expression pattern of SSTR1-5 mRNA in the central nervous system as was found by RT-PCR for the periphery. Such distinct SRIF receptor expression may contribute to the selective biological functions of the receptor subtypes.
European Journal of Pharmacology: Molecular Pharmacology, 1995
Somatostatin (SRIF) SS-1 binding sites were initially defined in radioligand binding studies perf... more Somatostatin (SRIF) SS-1 binding sites were initially defined in radioligand binding studies performed in rat brain cerebral cortex membranes using [125I]204-090 (a radiolabelled Tyr 3 analogue of SMS 201-995, octreotide). SRIF-1 recognition sites were defincd in binding studies performed with [125I]MK 678 (scglitide). Both SS-I and SRIF-1 sites were characterized by their high affinity for SRIF-14, SRIF-28 and for cyclic peptidcs such as octreotide and seglitide, in marked contrast to SSo2 and SRIF-2 sites which have very low affinity for these synthetic SRIF analogues. In the present study, SS-1 and SRIF-1 radioligand binding studies were performed in rat cortex membranes and compared to results obtained in cloned Chinese hamster ovary cells expressing human SSTR-2 receptors using [125I]204-090 and/or [125I]MK-678. The rank orders of affinity of a variety of SRIF analogues and synthetic pcptides for SS-1/SRIF-I binding sites and recombinant SSTR-2 receptors were very similar and correlated highly significantly (r = 0.94-0.99); by contrast, correlation between SS-1 and SSTR-5 (r = 0.44) or SSTR-3 binding (r = 0.07) was not significant. Autoradiographic studies were performed in rat brain using both radioligands [125I]204-090 and [1251]MK-678 and compared with the distribution of SSTR-2 receptor mRNA determined using in situ hybridization. A clear overlap was observed between the distribution of SSTR-2 mRNA and binding sites labelled with both radioligands. SSTR-2 receptor-mediated inhibition of forskolin-stimulated adenylate cyclase in Chines hamster ovary cells by a variety of SRIF analogues and short synthetic peptides displayed a rank order of potency highly similar to their rank order of affinity at SS-1/SRIF-I binding sites. It is concluded that SS-I and SRIF-1 binding sites respectively labelled with [125I]204-090 and [~25I]MK 678, both display the pharmacological profile of SSTR-2 receptors, that the distribution of [12511204-090 and [1251]MK-678 binding sites in rat brain is superimposable and largely comparable to that of SSTR-2 mRNA expression. It is also shown that neither [125I]204-090 nor [125I]MK-678 label SSTR-3 or SSTR-5 receptors in rat brain. Finally, it is demonstrated that SSTR-2 receptors can very efficiently couple to adenylate cyclase activity in an inhibitory manner.
Naunyn-schmiedebergs Archives of Pharmacology, 1994
In situ hybridization histochemistry was performed to analyse the distribution of the messenger R... more In situ hybridization histochemistry was performed to analyse the distribution of the messenger RNA (mRNA) of three putative somatostatin (SRIF) receptors in rat brain, using oligonucleotide probes derived from the cDNA coding for SSTR-1, SSTR-2, and SSTR-3 receptors. SSTR-1 signals were found in layers VVI of the cerebral cortex, in primary olfactory cortex, taenia tecta, subiculum, entorhinal cortex, granular layer of the dentate gyrus, amygdala and cerebellar nuclei. Signals for SSTR-2 were found in the frontal cerebral cortex (layers IV, V and VI), taenia tecta, claustrum, endopiriform nucleus, locus coeruleus, medial habenula, subiculum, granular cell layer of the dentate gyrus and amygdala. High levels of SSTR-3 hybridization were found in the olfactory bulb, primary olfactory cortex, islands of Calleja, medial habenula, amygdala, granular layer of the dentate gyrus, various thalamic and pontine nuclei and in the granular and Purkinje cell layers of the cerebellum. The distribution of the hybridization signals of the oligoprobes is consistent with the labelling of specific SRIF binding sites in rat brain. Especially, SSTR-2 and SSTR-1 oligos seem to label regions in which SS-1 and SS-2 receptors, respectively, have been previously characterized in autoradiographical studies. The situation is less clear with SSTR-3 mRNA, since SRIF binding in adult rats is usually low or absent in cerebellum, although some cerebellar nuclei appear to be labelled in the adult. The localization of SSTR-1, SSTR-2 and SSTR-3 mRNAs suggests that SRIF receptor subtypes in rat brain show profound differences in their distribution and are involved in a variety of central, in addition to neuroendocrine, functions.
Reservados todos los derechos. El contenido de esta obra está protegido por la Ley, que establece... more Reservados todos los derechos. El contenido de esta obra está protegido por la Ley, que establece penas de prisión y/o multas, además de las correspondientes indemnizaciones por daños y perjuicios, para quienes reprodujeren, plagiaren, distribuyeren o comunicaren públicamente, en todo o en parte, una obra literaria, artística o científica, o su transformación, interpretación o ejecución artística fijada en cualquier tipo de soporte o comunicada a través de cualquier medio, sin la preceptiva autorización. teléfono 91 393 88 88 www.alianzaeditorial.es ISBN: 84-206-7348-X Depósito legal: M. 49.308-2005 Impreso en Fernández Ciudad, S. L. Printed in Spain La dialéctica erística* es el arte de discutir, y de discutir de tal modo que uno siempre lleve razón1, es decir, per fas et nefas [justa o injustamente]**. Uno puede, pues, tener razón objetiva en el asunto mismo y sin embargo carecer de ella a ojos de los presentes, incluso a veces a los propios ojos. Ese es el caso cuando, por ejemplo, el adversario refuta mi prueba y esto se considera una refutación de la propia afirmación, para la cual puede no obstante haber * Entre los antiguos, lógica y dialéctica solían utilizarse como sinónimos; lo mismo ocurre con los modernos. ** La de erística no sería sino una palabra más dura para decir lo mismo. Aristóteles, según Diógenes Laercio, V, 28, consideró conjuntamente retórica y dialéctica, cuyo fin es la persuasión, TÓ 1. Utilizo por convención las expresiones «tener razón» y «llevar razón» para traducir, respectivamente, «Recht haben» y «Recht behalten». Schopenhauer emplea la primera para expresar el hecho de tener objetivamente razón; la segunda, para referirse a la técnica de imponerse en la discusión, con independencia de que se tenga o no razón en el asunto discutido.
Naunyn-schmiedebergs Archives of Pharmacology, 1996
The messenger RNA (mRNA) expression of somatostatin receptors sst1–5 was studied in human brain b... more The messenger RNA (mRNA) expression of somatostatin receptors sst1–5 was studied in human brain by in situ hybridization histochemistry using specific oligonucleotide probes. sst1 receptor mRNA was mainly found in the outer and intermediate layers of cerebral cortex, hippocampal formation (CA1, dentate gyrus, entorhinal cortex), hypothalamus, substantia nigra, medullary nuclei and dentate nucleus. sst2 transcripts were present in the deep layers of the cerebral cortex, amygdala, hippocampal formation (CA1, dentate gyrus, subiculum, entorhinal cortex), the granular layer of the cerebellum and pituitary. sst3 receptor mRNA was localized in the cerebral cortex, hippocampal formation (CA1, dentate gyrus), several medullary nuclei and the granule and possibly Purkinje cell layer of the cerebellum and at very low levels in the pituitary. sst4 receptor mRNA was absent in the cerebral cortex. Intermediate signals were observed in the dentate gyrus of the hippocampus and several medullary nuclei while an intense expression was found in the granule and Purkinje cell layer of cerebellum. sst5 transcripts were present in the pituitary and the granule layer of the cerebellum. The present results show that mRNAs of sst1–4 somatostatin receptors have distinct distribution patterns within the human brain, although there is overlap in several regions. sst5 receptor mRNA expression appears to be very low and restricted to the cerebellum and pituitary. The distribution pattern observed in the human brain was broadly similar to that reported previously in the rat brain. The high expression levels of at least two somatostatin receptor subtype mRNAs (sst2 and sst5) in the pituitary gland suggest that somatostatin may affect neuroendocrine functions via more than one receptor.
Somatostatin regulates endocrine and exocrine secretion, acts as a neurotransmitter/neuro-modulat... more Somatostatin regulates endocrine and exocrine secretion, acts as a neurotransmitter/neuro-modulator and possesses antiproliferative properties. These diverse physiological effects are mediated by G-protein coupled receptors of which at least five subtypes have been cloned (SSTR1-5). Here, we have investigated the tissue distribution pattern of mRNAs encoding the five SRIF receptor subtypes in the adult rat by RT-PCR analysis and in situ hybridization histochemistry. All five receptor subtypes were found to be expressed simultaneously in brain and pituitary by RT-PCR. Besides, the in situ hybridization results clearly show a distinct but overlapping expression pattern of SSTR1-5 mRNA in the central nervous system as was found by RT-PCR for the periphery. Such distinct SRIF receptor expression may contribute to the selective biological functions of the receptor subtypes.
European Journal of Pharmacology: Molecular Pharmacology, 1995
Somatostatin (SRIF) SS-1 binding sites were initially defined in radioligand binding studies perf... more Somatostatin (SRIF) SS-1 binding sites were initially defined in radioligand binding studies performed in rat brain cerebral cortex membranes using [125I]204-090 (a radiolabelled Tyr 3 analogue of SMS 201-995, octreotide). SRIF-1 recognition sites were defincd in binding studies performed with [125I]MK 678 (scglitide). Both SS-I and SRIF-1 sites were characterized by their high affinity for SRIF-14, SRIF-28 and for cyclic peptidcs such as octreotide and seglitide, in marked contrast to SSo2 and SRIF-2 sites which have very low affinity for these synthetic SRIF analogues. In the present study, SS-1 and SRIF-1 radioligand binding studies were performed in rat cortex membranes and compared to results obtained in cloned Chinese hamster ovary cells expressing human SSTR-2 receptors using [125I]204-090 and/or [125I]MK-678. The rank orders of affinity of a variety of SRIF analogues and synthetic pcptides for SS-1/SRIF-I binding sites and recombinant SSTR-2 receptors were very similar and correlated highly significantly (r = 0.94-0.99); by contrast, correlation between SS-1 and SSTR-5 (r = 0.44) or SSTR-3 binding (r = 0.07) was not significant. Autoradiographic studies were performed in rat brain using both radioligands [125I]204-090 and [1251]MK-678 and compared with the distribution of SSTR-2 receptor mRNA determined using in situ hybridization. A clear overlap was observed between the distribution of SSTR-2 mRNA and binding sites labelled with both radioligands. SSTR-2 receptor-mediated inhibition of forskolin-stimulated adenylate cyclase in Chines hamster ovary cells by a variety of SRIF analogues and short synthetic peptides displayed a rank order of potency highly similar to their rank order of affinity at SS-1/SRIF-I binding sites. It is concluded that SS-I and SRIF-1 binding sites respectively labelled with [125I]204-090 and [~25I]MK 678, both display the pharmacological profile of SSTR-2 receptors, that the distribution of [12511204-090 and [1251]MK-678 binding sites in rat brain is superimposable and largely comparable to that of SSTR-2 mRNA expression. It is also shown that neither [125I]204-090 nor [125I]MK-678 label SSTR-3 or SSTR-5 receptors in rat brain. Finally, it is demonstrated that SSTR-2 receptors can very efficiently couple to adenylate cyclase activity in an inhibitory manner.
Naunyn-schmiedebergs Archives of Pharmacology, 1994
In situ hybridization histochemistry was performed to analyse the distribution of the messenger R... more In situ hybridization histochemistry was performed to analyse the distribution of the messenger RNA (mRNA) of three putative somatostatin (SRIF) receptors in rat brain, using oligonucleotide probes derived from the cDNA coding for SSTR-1, SSTR-2, and SSTR-3 receptors. SSTR-1 signals were found in layers VVI of the cerebral cortex, in primary olfactory cortex, taenia tecta, subiculum, entorhinal cortex, granular layer of the dentate gyrus, amygdala and cerebellar nuclei. Signals for SSTR-2 were found in the frontal cerebral cortex (layers IV, V and VI), taenia tecta, claustrum, endopiriform nucleus, locus coeruleus, medial habenula, subiculum, granular cell layer of the dentate gyrus and amygdala. High levels of SSTR-3 hybridization were found in the olfactory bulb, primary olfactory cortex, islands of Calleja, medial habenula, amygdala, granular layer of the dentate gyrus, various thalamic and pontine nuclei and in the granular and Purkinje cell layers of the cerebellum. The distribution of the hybridization signals of the oligoprobes is consistent with the labelling of specific SRIF binding sites in rat brain. Especially, SSTR-2 and SSTR-1 oligos seem to label regions in which SS-1 and SS-2 receptors, respectively, have been previously characterized in autoradiographical studies. The situation is less clear with SSTR-3 mRNA, since SRIF binding in adult rats is usually low or absent in cerebellum, although some cerebellar nuclei appear to be labelled in the adult. The localization of SSTR-1, SSTR-2 and SSTR-3 mRNAs suggests that SRIF receptor subtypes in rat brain show profound differences in their distribution and are involved in a variety of central, in addition to neuroendocrine, functions.
Naunyn-schmiedebergs Archives of Pharmacology, 1996
The messenger RNA (mRNA) expression of somatostatin receptors sst1–5 was studied in human brain b... more The messenger RNA (mRNA) expression of somatostatin receptors sst1–5 was studied in human brain by in situ hybridization histochemistry using specific oligonucleotide probes. sst1 receptor mRNA was mainly found in the outer and intermediate layers of cerebral cortex, hippocampal formation (CA1, dentate gyrus, entorhinal cortex), hypothalamus, substantia nigra, medullary nuclei and dentate nucleus. sst2 transcripts were present in the deep layers of the cerebral cortex, amygdala, hippocampal formation (CA1, dentate gyrus, subiculum, entorhinal cortex), the granular layer of the cerebellum and pituitary. sst3 receptor mRNA was localized in the cerebral cortex, hippocampal formation (CA1, dentate gyrus), several medullary nuclei and the granule and possibly Purkinje cell layer of the cerebellum and at very low levels in the pituitary. sst4 receptor mRNA was absent in the cerebral cortex. Intermediate signals were observed in the dentate gyrus of the hippocampus and several medullary nuclei while an intense expression was found in the granule and Purkinje cell layer of cerebellum. sst5 transcripts were present in the pituitary and the granule layer of the cerebellum. The present results show that mRNAs of sst1–4 somatostatin receptors have distinct distribution patterns within the human brain, although there is overlap in several regions. sst5 receptor mRNA expression appears to be very low and restricted to the cerebellum and pituitary. The distribution pattern observed in the human brain was broadly similar to that reported previously in the rat brain. The high expression levels of at least two somatostatin receptor subtype mRNAs (sst2 and sst5) in the pituitary gland suggest that somatostatin may affect neuroendocrine functions via more than one receptor.
Somatostatin regulates endocrine and exocrine secretion, acts as a neurotransmitter/neuro-modulat... more Somatostatin regulates endocrine and exocrine secretion, acts as a neurotransmitter/neuro-modulator and possesses antiproliferative properties. These diverse physiological effects are mediated by G-protein coupled receptors of which at least five subtypes have been cloned (SSTR1-5). Here, we have investigated the tissue distribution pattern of mRNAs encoding the five SRIF receptor subtypes in the adult rat by RT-PCR analysis and in situ hybridization histochemistry. All five receptor subtypes were found to be expressed simultaneously in brain and pituitary by RT-PCR. Besides, the in situ hybridization results clearly show a distinct but overlapping expression pattern of SSTR1-5 mRNA in the central nervous system as was found by RT-PCR for the periphery. Such distinct SRIF receptor expression may contribute to the selective biological functions of the receptor subtypes.
European Journal of Pharmacology: Molecular Pharmacology, 1995
Somatostatin (SRIF) SS-1 binding sites were initially defined in radioligand binding studies perf... more Somatostatin (SRIF) SS-1 binding sites were initially defined in radioligand binding studies performed in rat brain cerebral cortex membranes using [125I]204-090 (a radiolabelled Tyr 3 analogue of SMS 201-995, octreotide). SRIF-1 recognition sites were defincd in binding studies performed with [125I]MK 678 (scglitide). Both SS-I and SRIF-1 sites were characterized by their high affinity for SRIF-14, SRIF-28 and for cyclic peptidcs such as octreotide and seglitide, in marked contrast to SSo2 and SRIF-2 sites which have very low affinity for these synthetic SRIF analogues. In the present study, SS-1 and SRIF-1 radioligand binding studies were performed in rat cortex membranes and compared to results obtained in cloned Chinese hamster ovary cells expressing human SSTR-2 receptors using [125I]204-090 and/or [125I]MK-678. The rank orders of affinity of a variety of SRIF analogues and synthetic pcptides for SS-1/SRIF-I binding sites and recombinant SSTR-2 receptors were very similar and correlated highly significantly (r = 0.94-0.99); by contrast, correlation between SS-1 and SSTR-5 (r = 0.44) or SSTR-3 binding (r = 0.07) was not significant. Autoradiographic studies were performed in rat brain using both radioligands [125I]204-090 and [1251]MK-678 and compared with the distribution of SSTR-2 receptor mRNA determined using in situ hybridization. A clear overlap was observed between the distribution of SSTR-2 mRNA and binding sites labelled with both radioligands. SSTR-2 receptor-mediated inhibition of forskolin-stimulated adenylate cyclase in Chines hamster ovary cells by a variety of SRIF analogues and short synthetic peptides displayed a rank order of potency highly similar to their rank order of affinity at SS-1/SRIF-I binding sites. It is concluded that SS-I and SRIF-1 binding sites respectively labelled with [125I]204-090 and [~25I]MK 678, both display the pharmacological profile of SSTR-2 receptors, that the distribution of [12511204-090 and [1251]MK-678 binding sites in rat brain is superimposable and largely comparable to that of SSTR-2 mRNA expression. It is also shown that neither [125I]204-090 nor [125I]MK-678 label SSTR-3 or SSTR-5 receptors in rat brain. Finally, it is demonstrated that SSTR-2 receptors can very efficiently couple to adenylate cyclase activity in an inhibitory manner.
Naunyn-schmiedebergs Archives of Pharmacology, 1994
In situ hybridization histochemistry was performed to analyse the distribution of the messenger R... more In situ hybridization histochemistry was performed to analyse the distribution of the messenger RNA (mRNA) of three putative somatostatin (SRIF) receptors in rat brain, using oligonucleotide probes derived from the cDNA coding for SSTR-1, SSTR-2, and SSTR-3 receptors. SSTR-1 signals were found in layers VVI of the cerebral cortex, in primary olfactory cortex, taenia tecta, subiculum, entorhinal cortex, granular layer of the dentate gyrus, amygdala and cerebellar nuclei. Signals for SSTR-2 were found in the frontal cerebral cortex (layers IV, V and VI), taenia tecta, claustrum, endopiriform nucleus, locus coeruleus, medial habenula, subiculum, granular cell layer of the dentate gyrus and amygdala. High levels of SSTR-3 hybridization were found in the olfactory bulb, primary olfactory cortex, islands of Calleja, medial habenula, amygdala, granular layer of the dentate gyrus, various thalamic and pontine nuclei and in the granular and Purkinje cell layers of the cerebellum. The distribution of the hybridization signals of the oligoprobes is consistent with the labelling of specific SRIF binding sites in rat brain. Especially, SSTR-2 and SSTR-1 oligos seem to label regions in which SS-1 and SS-2 receptors, respectively, have been previously characterized in autoradiographical studies. The situation is less clear with SSTR-3 mRNA, since SRIF binding in adult rats is usually low or absent in cerebellum, although some cerebellar nuclei appear to be labelled in the adult. The localization of SSTR-1, SSTR-2 and SSTR-3 mRNAs suggests that SRIF receptor subtypes in rat brain show profound differences in their distribution and are involved in a variety of central, in addition to neuroendocrine, functions.
Reservados todos los derechos. El contenido de esta obra está protegido por la Ley, que establece... more Reservados todos los derechos. El contenido de esta obra está protegido por la Ley, que establece penas de prisión y/o multas, además de las correspondientes indemnizaciones por daños y perjuicios, para quienes reprodujeren, plagiaren, distribuyeren o comunicaren públicamente, en todo o en parte, una obra literaria, artística o científica, o su transformación, interpretación o ejecución artística fijada en cualquier tipo de soporte o comunicada a través de cualquier medio, sin la preceptiva autorización. teléfono 91 393 88 88 www.alianzaeditorial.es ISBN: 84-206-7348-X Depósito legal: M. 49.308-2005 Impreso en Fernández Ciudad, S. L. Printed in Spain La dialéctica erística* es el arte de discutir, y de discutir de tal modo que uno siempre lleve razón1, es decir, per fas et nefas [justa o injustamente]**. Uno puede, pues, tener razón objetiva en el asunto mismo y sin embargo carecer de ella a ojos de los presentes, incluso a veces a los propios ojos. Ese es el caso cuando, por ejemplo, el adversario refuta mi prueba y esto se considera una refutación de la propia afirmación, para la cual puede no obstante haber * Entre los antiguos, lógica y dialéctica solían utilizarse como sinónimos; lo mismo ocurre con los modernos. ** La de erística no sería sino una palabra más dura para decir lo mismo. Aristóteles, según Diógenes Laercio, V, 28, consideró conjuntamente retórica y dialéctica, cuyo fin es la persuasión, TÓ 1. Utilizo por convención las expresiones «tener razón» y «llevar razón» para traducir, respectivamente, «Recht haben» y «Recht behalten». Schopenhauer emplea la primera para expresar el hecho de tener objetivamente razón; la segunda, para referirse a la técnica de imponerse en la discusión, con independencia de que se tenga o no razón en el asunto discutido.
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