Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aims of the study were to determine; (1) whether activation of serotonin (5-HT) receptors in the brain increases renin secretion, and (2) whether the hypertensive effects of a 5-HT agonist and 5-HT releaser obscure their ability to stimulate renin release. Various drugs that increase serotonergic neuro-transmission can activate the secretion of renin from the kidneys. Many of these drugs can also elevate blood pressure. Changes in blood pressure can alter renin secretion by activating renal baroreceptor mechanisms, so that a decrease in perfusion pressure will increase renin secretion and vice versa. To address the first objective, the 5-HT agonist RU 24969 (0, 10, 100 and 200 micrograms/kg) and the 5-HT releaser p-chloroamphetamine (0, 50, 500 and 1,000 micrograms/kg) were injected intracerebroventricularly (ICV) at doses lower than those that are peripherally effective. ICV injection of RU 24969 dose-dependently increased plasma levels of renin. ICV injection of the 5-HT2A/5-HT2C antagonist LY53857 (50 micrograms/kg) inhibited the renin response to peripherally injected RU 24969 (0, 1, 5 and 10 mg/kg i.p.), suggesting that 5-HT2A/5-HT2C receptors in the brain mediate the effect of peripherally injected RU 24969 on renin secretion. In contrast, ICV injection of p-chloroamphetamine decreased renin secretion. To determine whether hypertensive actions could account for the differences between RU 24969 and p-chloroamphetamine, we measured the effects of both p-chloroamphetamine and RU 24969 on blood pressure and heart rate. ICV injection of p-chloroamphetamine (1,000 micrograms/kg) produced a large rise of 44 mm Hg at 2 min and 25 mm Hg at 5 min after injection, while ICV injection of RU 24969 (200 micrograms/kg) caused a slower and smaller blood pressure elevation of 18 mm Hg at 5 min after injection. To determine whether the hypertensive effects of both RU 24969 and p-chloroamphetamine could mask their effects on renin secretion, rats were pretreated with the alpha 1 antagonist prazosin. Administration of prazosin (1 mg/kg s.c.), which prevents the hypertensive effects of p-chloroamphetamine, exposed a stimulatory effect of ICV-injected p-chloroamphetamine (500 micrograms/kg) on renin secretion and potentiated the effect of RU 24969 (5 mg/kg i.p.) on renin release. In conclusion, these data suggest that both RU 24969 and p-chloroamphetamine increase renin secretion through central 5-HT receptors, and that these effects are partially obscured by their hypertensive actions.
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PMID:Central stimulation of renin secretion through serotonergic, noncardiovascular mechanisms. 796 78

The influence of cocaine exposure on serotonergic neurons and postsynaptic 5-HT1A receptor-mediated responses was evaluated by measuring neuroendocrine responses to a serotonin (5-HT) releaser or a 5-HT1A agonist. Male rats received cocaine (15 mg/kg, i.p.) or saline twice daily for 7 days. Forty-two hr after the final cocaine injection, the 5-HT releaser d-fenfluramine (0, 0.2, 0.6, 2, or 5 mg/kg, i.p.) or the 5-HT1A agonist, 8-OH-DPAT (0, 10, 50, 200 or 500 micrograms/kg, s.c.) were administered. Blood samples were then collected for analysis of plasma ACTH, prolactin, and renin concentrations. The ACTH responses to d-fenfluramine and 8-OH-DPAT were inhibited in cocaine pretreated rats. However, the prolactin responses to d-fenfluramine and 8-OH-DPAT were not significantly modified by cocaine exposure. Additionally, the renin response to d-fenfluramine was unaltered by repeated cocaine administration, while 8-OH-DPAT did not alter renin secretion in either pretreatment group. In contrast to published reports which show that cocaine exposure produces supersensitive 5-HT2A and/or 5-HT2C receptor-mediated responses, the present data suggest that repeated cocaine exposure produces subsensitivity to at least some postsynaptic 5-HT1A receptors. Cocaine-induced deficits in the ACTH response to 5-HT releasers may reflect 5-HT1A receptor subsensitivity, but presynaptic deficits cannot be excluded. Examination of the ACTH response to 5-HT1A agonists may represent a valuable approach to determine deficits in 5-HT function in human cocaine abusers.
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PMID:Repeated cocaine exposure inhibits the adrenocorticotropic hormone response to the serotonin releaser d-fenfluramine and the 5-HT1A agonist, 8-OH-DPAT. 798 71

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are effective drugs for the treatment of several neuropsychiatric disorders associated with reduced serotonergic function. Serotonergic neurons play an important role in the regulation of neuroendocrine function. This review will discuss the acute and chronic effects of SSRIs on neuroendocrine function. Acute administration of SSRIs increases the secretion of several hormones, but chronic treatment with SSRIs does not alter basal blood levels of hormones. However, adaptive changes are induced by long-term treatment with SSRIs in serotonergic, noradrenergic and peptidergic neural function. These adaptive changes, particularly in the function of specific post-synaptic receptor systems, can be examined from altered adrenocorticotrophic hormone (ACTH), cortisol, oxytocin, vasopressin, prolactin, growth hormone (GH) and renin responses to challenges with specific agonists. Neuroendocrine challenge tests both in experimental animals and in humans indicate that chronic SSRIs produce an increase in serotonergic terminal function, accompanied by desensitization of post-synaptic 5-HT1A receptor-mediated ACTH, cortisol, GH and oxytocin responses, and by supersensitivity of post-synaptic 5-HT2A (and/or 5-HT2C) receptor-mediated secretion of hormones. Chronic exposure to SSRIs does not alter the neuroendocrine stress-response and produces inconsistent changes in alpha2 adrenoceptor-mediated GH secretion. Overall, the effects of SSRIs on neuroendocrine function are dependent on adaptive changes in specific neurotransmitter systems that regulate the secretion of specific hormones.
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PMID:Selective serotonin reuptake inhibitors and neuroendocrine function. 1050 38

The present study determined whether the serotonin2A (5-HT2A) receptors in the hypothalamic paraventricular nucleus mediate the neuroendocrine responses to a peripheral injection of the 5-HT2A/2C receptor agonist (-)DOI [(-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]. The 5-HT2A receptor antagonist MDL100,907 ((+/-)-alpha(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol), the 5-HT2C receptor antagonist SB-242084 (6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline), or vehicle were microinjected bilaterally through a chronically implanted double-barreled cannula into the hypothalamic paraventricular nucleus 15 min before a peripheral injection of (-)DOI in conscious rats. (-)DOI significantly elevated plasma levels of oxytocin, prolactin, ACTH, corticosterone, and renin. Neither the 5-HT2A receptor antagonist nor the 5-HT2C receptor antagonist, injected alone, altered the basal levels of these hormones. MDL100,907 (0.748, 7.48, and 18.7 nmol) dose dependently inhibited the (-)DOI-induced increase in all of the hormones except corticosterone. In contrast, SB-242084 (10 nmol) did not inhibit (-)DOI-increased hormone levels. To confirm the presence of 5-HT2A receptors in the hypothalamic paraventricular nucleus, 5-HT2A receptors were mapped using immunohistochemistry. Densely labeled magnocellular neurons were observed throughout the anterior and posterior magnocellular subdivisions of the hypothalamic paraventricular nucleus. Moderately to densely labeled cells were also observed in parvicellular regions. Thus, it is likely that 5-HT2A receptors are present on neuroendocrine cells in the hypothalamic paraventricular nucleus. These data provide the first direct evidence that neuroendocrine responses to a peripheral injection of (-)DOI are predominantly mediated by activation of 5-HT2A receptors in the hypothalamic paraventricular nucleus.
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PMID:Evidence that 5-HT2A receptors in the hypothalamic paraventricular nucleus mediate neuroendocrine responses to (-)DOI. 1241 89