The term modernism refers to the radical shift in aesthetic and cultural sensibilities evident in... more The term modernism refers to the radical shift in aesthetic and cultural sensibilities evident in the art and literature of the post-World War I period. Modernism marks a distinctive break with Victorian bourgeois morality; rejecting nineteenth-century optimism, they presented a profoundly pessimistic picture of a culture in disarray. This despair often results in an apparent apathy and moral relativism.
The term modernism refers to the radical shift in aesthetic and cultural sensibilities evident in... more The term modernism refers to the radical shift in aesthetic and cultural sensibilities evident in the art and literature of the post-World War I period. Modernism marks a distinctive break with Victorian bourgeois morality; rejecting nineteenth-century optimism, they presented a profoundly pessimistic picture of a culture in disarray. This despair often results in an apparent apathy and moral relativism.
Journal of Receptors and Signal Transduction, 1986
In rat renal medullary membranes, we have examined modulatory effects of guanine nucleotides on b... more In rat renal medullary membranes, we have examined modulatory effects of guanine nucleotides on binding of arginine8 vasopressin (AVP) to its receptor. Equilibrium binding studies analyzed by an iterative curve fitting program revealed an interaction of (3H) AVP with a single class of binding sites with a dissociation constant of 1.4 +/- 0.2 nM and a binding site concentration of 201 +/- 37 fmol/mg protein (n = 6). With the addition of 100 microM guanylyl-imidodiphosphate (Gpp(NH)p), the binding site concentration was significantly (p less than 0.01) reduced to 151 +/- 36 fmol/mg protein with no change in receptor affinity. The nonhydrolyzable analogues, guanosine-5'-0-(3-thiophosphate) and Gpp(NH)p were the most potent inhibitors of (3H) AVP binding. Guanosine 5'-triphosphate and guanosine-5'-diphosphate were both relatively poor inhibitors. Guanosine-5'-monophosphate and adenosine 5'-triphosphate did not inhibit (3H) AVP binding at concentrations up to 100 microM. Furthermore, 100 microM Gpp(NH)p accelerated the dissociation of (3H) AVP from the receptor. We conclude that guanine nucleotides are important modulators of AVP binding to the V2 receptor subtype in the renal medulla.
Vasopressin (VP) neurons in the bed nucleus of the stria terminalis (BNST) and medial amygdala (A... more Vasopressin (VP) neurons in the bed nucleus of the stria terminalis (BNST) and medial amygdala (AME) are sensitive to changes in circulating levels of testosterone (T). To determine whether these cells are responsive to changes in glucocorticoid levels, in situ hybridization and quantitative autoradiography were used to measure VP mRNA in cells of the BNST and AME in rats that were adrenalectomized (ADX; 14 days) or ADX with dexamethasone (DEX) replacement. These treatments produced the predicted changes in VP gene expression in the medial parvocellular group of the paraventricular nucleus. The VP mRNA content within cells of the BNST or AME was unaffected by adrenalectomy. Treatment with DEX significantly decreased both the number and labeling intensity of VP cells in the BNST and AME. Measurement of plasma T in these animals showed that DEX treatment significantly lowered mean T levels compared with those in either sham-operated or ADX animals. Adrenalectomy alone did not significantly alter T levels. To determine whether DEX influenced VP gene expression via a glucocorticoid action or secondarily by a suppression of T, the above experiment was repeated with groups that were castrated and implanted with Silastic capsules containing T to maintain physiological levels of T. Administration of DEX again decreased both VP cell number and labeling intensity of cells in the BNST and AME in sham-implanted animals. However, VP gene expression was unaffected in those animals that received T capsules. Administration of corticosterone did not alter T levels or the number of cells in the BNST or AME. These results suggest that, in contrast to paraventricular nucleus neurons, adrenalectomy (14 days) is not a potent stimulus in altering VP activity in the BNST or AME. The DEX-induced decrease in VP gene expression is mediated by a secondary suppression of T levels. These results support the finding that gonadal steroids are essential in maintaining the biosynthetic integrity of VP neurons in the BNST and AME.
Proceedings of The National Academy of Sciences, 1997
The antipsychotic drug, haloperidol, elicits the expression of neurotensin and c-fos mRNA in the ... more The antipsychotic drug, haloperidol, elicits the expression of neurotensin and c-fos mRNA in the dorsal lateral region of the striatum and produces an acute cataleptic response in rodents that correlates with the motor side effects of haloperidol in humans. Mice harboring a targeted disruption of the RIIβ subunit of protein kinase A have a profound deficit in cAMP-stimulated kinase activity in the striatum. When treated with haloperidol, RIIβ mutant mice fail to induce either c-fos or neurotensin mRNA and the acute cataleptic response is blocked. However, both wild-type and mutant mice become cataleptic when neurotensin peptide is directly injected into the lateral ventricle, demonstrating that the kinase deficiency does not interfere with the action of neurotensin but rather its synthesis and release. These results establish a direct role for protein kinase A as a mediator of haloperidol induced gene induction and cataleptic behavior.
The term modernism refers to the radical shift in aesthetic and cultural sensibilities evident in... more The term modernism refers to the radical shift in aesthetic and cultural sensibilities evident in the art and literature of the post-World War I period. Modernism marks a distinctive break with Victorian bourgeois morality; rejecting nineteenth-century optimism, they presented a profoundly pessimistic picture of a culture in disarray. This despair often results in an apparent apathy and moral relativism.
The term modernism refers to the radical shift in aesthetic and cultural sensibilities evident in... more The term modernism refers to the radical shift in aesthetic and cultural sensibilities evident in the art and literature of the post-World War I period. Modernism marks a distinctive break with Victorian bourgeois morality; rejecting nineteenth-century optimism, they presented a profoundly pessimistic picture of a culture in disarray. This despair often results in an apparent apathy and moral relativism.
Journal of Receptors and Signal Transduction, 1986
In rat renal medullary membranes, we have examined modulatory effects of guanine nucleotides on b... more In rat renal medullary membranes, we have examined modulatory effects of guanine nucleotides on binding of arginine8 vasopressin (AVP) to its receptor. Equilibrium binding studies analyzed by an iterative curve fitting program revealed an interaction of (3H) AVP with a single class of binding sites with a dissociation constant of 1.4 +/- 0.2 nM and a binding site concentration of 201 +/- 37 fmol/mg protein (n = 6). With the addition of 100 microM guanylyl-imidodiphosphate (Gpp(NH)p), the binding site concentration was significantly (p less than 0.01) reduced to 151 +/- 36 fmol/mg protein with no change in receptor affinity. The nonhydrolyzable analogues, guanosine-5'-0-(3-thiophosphate) and Gpp(NH)p were the most potent inhibitors of (3H) AVP binding. Guanosine 5'-triphosphate and guanosine-5'-diphosphate were both relatively poor inhibitors. Guanosine-5'-monophosphate and adenosine 5'-triphosphate did not inhibit (3H) AVP binding at concentrations up to 100 microM. Furthermore, 100 microM Gpp(NH)p accelerated the dissociation of (3H) AVP from the receptor. We conclude that guanine nucleotides are important modulators of AVP binding to the V2 receptor subtype in the renal medulla.
Vasopressin (VP) neurons in the bed nucleus of the stria terminalis (BNST) and medial amygdala (A... more Vasopressin (VP) neurons in the bed nucleus of the stria terminalis (BNST) and medial amygdala (AME) are sensitive to changes in circulating levels of testosterone (T). To determine whether these cells are responsive to changes in glucocorticoid levels, in situ hybridization and quantitative autoradiography were used to measure VP mRNA in cells of the BNST and AME in rats that were adrenalectomized (ADX; 14 days) or ADX with dexamethasone (DEX) replacement. These treatments produced the predicted changes in VP gene expression in the medial parvocellular group of the paraventricular nucleus. The VP mRNA content within cells of the BNST or AME was unaffected by adrenalectomy. Treatment with DEX significantly decreased both the number and labeling intensity of VP cells in the BNST and AME. Measurement of plasma T in these animals showed that DEX treatment significantly lowered mean T levels compared with those in either sham-operated or ADX animals. Adrenalectomy alone did not significantly alter T levels. To determine whether DEX influenced VP gene expression via a glucocorticoid action or secondarily by a suppression of T, the above experiment was repeated with groups that were castrated and implanted with Silastic capsules containing T to maintain physiological levels of T. Administration of DEX again decreased both VP cell number and labeling intensity of cells in the BNST and AME in sham-implanted animals. However, VP gene expression was unaffected in those animals that received T capsules. Administration of corticosterone did not alter T levels or the number of cells in the BNST or AME. These results suggest that, in contrast to paraventricular nucleus neurons, adrenalectomy (14 days) is not a potent stimulus in altering VP activity in the BNST or AME. The DEX-induced decrease in VP gene expression is mediated by a secondary suppression of T levels. These results support the finding that gonadal steroids are essential in maintaining the biosynthetic integrity of VP neurons in the BNST and AME.
Proceedings of The National Academy of Sciences, 1997
The antipsychotic drug, haloperidol, elicits the expression of neurotensin and c-fos mRNA in the ... more The antipsychotic drug, haloperidol, elicits the expression of neurotensin and c-fos mRNA in the dorsal lateral region of the striatum and produces an acute cataleptic response in rodents that correlates with the motor side effects of haloperidol in humans. Mice harboring a targeted disruption of the RIIβ subunit of protein kinase A have a profound deficit in cAMP-stimulated kinase activity in the striatum. When treated with haloperidol, RIIβ mutant mice fail to induce either c-fos or neurotensin mRNA and the acute cataleptic response is blocked. However, both wild-type and mutant mice become cataleptic when neurotensin peptide is directly injected into the lateral ventricle, demonstrating that the kinase deficiency does not interfere with the action of neurotensin but rather its synthesis and release. These results establish a direct role for protein kinase A as a mediator of haloperidol induced gene induction and cataleptic behavior.
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