Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) produced dose-related increases in plasma concentrations of prolactin, adrenocorticotropic hormone (ACTH) and corticosterone but not growth hormone in rats. Pretreatment with metergoline (serotonin, 5-HT1/5-HT2 antagonist), ritanserin and mianserin (5-HT2A/5-HT2C antagonists) significantly attenuated DOM-induced increases in prolactin, ACTH and corticosterone, whereas mesulergine (5-HT2A/5-HT2C antagonist) pretreatment significantly attenuated DOM-induced increases in plasma prolactin and ACTH but not corticosterone. Pretreatment with propranolol (beta adrenoceptor antagonist that also has high binding affinity for 5-HT1A, 5-HT1B and 5-HT2C sites), MDL-72222 and ondansetron (5-HT3 antagonists) attenuated DOM's effect on plasma prolactin, but did not attenuate DOM-induced increases in either ACTH or corticosterone. On the other hand, spiperone (5-HT1A/5-HT2A/D2 antagonist) pretreatment significantly attenuated DOM-induced increases in ACTH but not corticosterone. These findings demonstrate involvement of 5-HT2A/5-HT2C and 5-HT3 receptors in mediating DOM-induced increases in plasma prolactin, whereas DOM-induced increases in ACTH appear to be mediated by stimulation of 5-HT2A receptors. DOM-induced corticosterone secretion appears to be mediated by stimulation of 5-HT2A and/or 5-HT2C receptors. DOM does not affect growth hormone secretion in rats.
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PMID:Role of various 5-HT receptor subtypes in mediating neuroendocrine effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in rats. 796 7

The present study had two objectives: (1) to provide information on neuroendocrine challenge tests that can lead to diagnostic tests in humans; and (2) to confirm our previous observation that chronic fluoxetine selectively inhibits serotonin (5-HT1A) receptor function. We determined the effect of chronic fluoxetine and desipramine (DMI) on the hormone response to ipsapirone, a 5-HT1A agonist and a potential anxiolytic drug. Ipsapirone increased oxytocin, adrenocorticotropic hormone (ACTH), corticosterone, and prolactin, but not renin or vasopressin concentrations in plasma. Chronic fluoxetine, but not DMI, significantly inhibited the effect of ipsapirone on plasma oxytocin, ACTH and corticosterone concentrations. Chronic fluoxetine also reduced the Bmax for 3H-8-hydroxy-2-(dipropylamino) tetralin (3H-8-OH-DPAT) labelled 5-HT1A receptors in the midbrain. Neither antidepressant altered the density or affinity of 5-HT uptake sites. In conclusion, the present results confirm our previous results using 8-OH-DPAT as a challenge, and suggest that chronic 5-HT uptake inhibition results in adaptive changes leading to decreased function of the 5-HT1A receptor system. Finally, because ipsapirone may be administered to humans, it might be usable to evaluate 5-HT1A receptor function in depressed patients.
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PMID:Attenuation of hormone responses to the 5-HT1A agonist ipsapirone by long-term treatment with fluoxetine, but not desipramine, in male rats. 799 56

Treatment of rats with the serotonin 5-HT1A agonist 8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT, 1 mg/kg s.c.) markedly elevated plasma levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH) and prolactin (PRL); the levels of growth hormone were unaffected. Pretreatment with the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 6 mg/kg s.c.) greatly attenuated the increase in plasma CORT produced by 8-OH-DPAT (0.3 mg/kg s.c.). Prevention of EEDQ-induced 5-HT1A receptor inactivation by prior treatment with the reversible mixed 5-HT1A/beta-adrenergic antagonist (+/-)pinodolol (30 mg/kg s.c.) blocked the reduction of the CORT response to 8-OH-DPAT. In contrast, prevention of EEDQ-induced inactivation of 5-HT2, alpha-1- and alpha-2-adrenergic and D1 and D2 dopamine receptors by a cocktail of selective antagonists of these receptors did not block the attenuation of the CORT response to 8-OH-DPAT. Dose-response curves were obtained for 8-OH-DPAT (0.01-3 mg/kg s.c.)-induced elevation of plasma CORT, ACTH and PRL after treatment (24 hr earlier) with vehicle or EEDQ (6 mg/kg s.c.) and analyzed for the extent of receptor reserve. Whereas substantial receptor reserves were observed for the 8-OH-DPAT rise in plasma CORT (80%) and ACTH (50%), no receptor reserve was seen for the increase in plasma PRL. The results are discussed with regard to potential differences in the receptors, G proteins, effectors and/or stoichiometric relationships between these components of the signal transduction pathway, leading to elevation of these plasma hormones after treatment with 8-OH-DPAT.
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PMID:Differential receptor reserve for 5-HT1A receptor-mediated regulation of plasma neuroendocrine hormones. 799 33

The present study investigated the consequences of prenatal cocaine exposure on central serotonin (5-HT) 5-HT1A receptor-mediated function in prepubescent male and female progeny. Pregnant rats received saline or cocaine (15 mg/kg s.c.) twice daily from gestational day 13 through 20. All litters were fostered to nontreated lactating dams. Cocaine did not alter weight gain during pregnancy and did not affect progeny weight at birth or at postnatal day 28. Male and female progeny were tested at a prepubescent age (postnatal day 28) by measuring 1) the stimulation of adrenocorticotropic hormone, corticosterone and renin by a maximally effective dose (0.5 mg/kg s.c.) of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT); and 2) [3H]8-OH-DPAT-labeled 5-HT1A receptors and [3H]paroxetine-labeled 5-HT uptake sites in hypothalamus, cortex and midbrain. Basal hormone levels were unaffected by prenatal cocaine exposure. However, prenatal cocaine exposure significantly potentiated the adrenocorticotropic hormone (+28%) and renin (+53%) responses to 8-OH-DPAT in male but not female progeny. In contrast, the corticosterone response to 8-OH-DPAT was not significantly altered in either male or female progeny. Likewise, the number of 5-HT1A receptors and 5-HT uptake sites in the cortex, midbrain and hypothalamus were unaffected by prenatal cocaine exposure. These data demonstrate that prenatal cocaine exposure can potentiate brain 5-HT1A receptor-mediated function in progeny and that alterations in hypothalamic 5-HT1A function are gender specific. These data suggest the possibility that prenatal cocaine may increase 5-HT1A receptor function in extrahypothalamic brain regions.
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PMID:Potentiation of 5-HT1A receptor-mediated neuroendocrine responses in male but not female rat progeny after prenatal cocaine: evidence for gender differences. 799 58

This study tested whether a new serotonin (5-HT1B) agonist, 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxy-pyrrolo[3,2-b]pyridine (CP-93,129), could be used to study the potential role of 5-HT1B receptors in the secretion of adrenocorticotropic hormone (ACTH), prolactin, and renin. CP-93,129 has a high affinity for 5-HT1B receptors but low affinity for other 5-HT receptor subtypes. In addition, CP-93,129 does not readily cross the blood-brain barrier. The secretion of ACTH, prolactin, and renin is known to be increased after activation of 5-HT receptors. ICV injections of CP-93,129 (100 micrograms/kg) increased the plasma concentrations of ACTH, prolactin, and renin. CP-93,129 also increased blood pressure and reduced heart rate. To determine whether these effects of CP-93,129 are centrally mediated, we compared them with IP injection of the same dose of CP-93,129. IP-injected CP-93,129 did not alter blood pressure or heart rate and did not elevate plasma prolactin and renin concentrations. To determine whether 5-HT1B receptors mediate the central effects of CP-93,129, rats were pretreated with the 5-HT antagonists l-propranolol or metergoline prior to ICV injections of doses of CP-93,129 (0-100 micrograms/kg). The 5-HT1A/1B/2A/2C antagonist metergoline (0.5 mg/kg, IP) failed to inhibit the CP-93,129-induced elevation of ACTH, prolactin, or renin concentrations. In contrast, the 5-HT1A/1B/beta antagonist l-propranolol (20 micrograms/kg, ICV) inhibited the renin but not the ACTH or prolactin responses to ICV CP-93,129.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ICV injection of the serotonin 5-HT1B agonist CP-93,129 increases the secretion of ACTH, prolactin, and renin and increases blood pressure by nonserotonergic mechanisms. 809 Aug 11

The RN46A cell line was derived from embryonic day 13 rat medullary raphe cells by infection with a retrovirus encoding the temperature-sensitive mutant of SV40 large T antigen (tsT-ag). The RN46A cell line is neuronally restricted and constitutively differentiates following a shift to nonpermissive temperature. Differentiated RN46A cells express low levels of tryptophan hydroxylase (TPH) but no detectable levels of serotonin (5-HT). Treatment of cultures with the adrenocorticotropic hormone peptide ACTH4-10 up-regulates the expression of TPH immunoreactivity in differentiated RN46A cells, but 5-HT synthesis requires initial treatment with ACTH4-10, followed by partial membrane depolarizing conditions. Up-regulation of TPH by ACTH4-10 is apparently due to activation of adenylate cyclase, whereas the increased 5-HT synthesis with membrane depolarization can be blocked with the voltage-sensitive Ca(2+)-channel blockers nifedipine and omega-conotoxin. ACTH4-10 treatment also markedly up-regulates the expression of the 5-HT reuptake transporter, as do dibutyryl cyclic AMP and forskolin; chronic membrane depolarization has no effect on 5-HT reuptake. The expression of the high-affinity 5-HT1A receptor is increased threefold by ACTH4-10 treatment during differentiation and fivefold by differentiation under partial membrane depolarizing conditions. Combining ACTH4-10 treatment and membrane depolarization does not increase expression of the 5-HT1A receptor further. 5-HT release is constitutive in ACTH-treated RN46A cells and linked to spontaneous synaptic vesicle fusion in RN46A cells. Considered with previous results, these data indicate that multiple effectors, ACTH, brain-derived neurotrophic factor, and membrane depolarization, have both distinct and overlapping effects that regulate specific elements of the serotonergic neuronal phenotype during differentiation and maturation.
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PMID:Adrenocorticotropic hormone activation of adenylate cyclase in raphe neurons: multiple regulatory pathways control serotonergic neuronal differentiation. 859 7

The effects of the selective 5-HT1A receptor agonist flesinoxan on neuroendocrine function, temperature, and behavior were assessed in male healthy volunteers using a double-blind, placebo-controlled crossover design. Flesinoxan (7 and 14 micrograms/kg), administered intravenously in 11 healthy volunteers, elicited a dose-related decrease in body temperature and increases in growth hormone, adrenocorticotropic hormone (ACTH), cortisol, and prolactin plasma levels. In a second independent study, 12 healthy volunteers were pretreated sequentially, at one-week intervals, with either the 5-HT1A antagonist pindolol (30 mg, PO), the nonselective 5-HT1/2 antagonist methysergide (4 mg, PO), or placebo, prior to being administered flesinoxan (1 mg, IV). The growth hormone response to flesinoxan was blocked by pindolol but not by methysergide, whereas the prolactin response was blocked by methysergide but not by pindolol. The ACTH and cortisol responses to flesinoxan were potentiated by methysergide. The flesinoxan-induced hypothermia was attenuated by both methysergide and pindolol, although the latter effects did not reach statistical significance. The present results suggest that the growth hormone response and the hypothermic response to the intravenous infusion of flesinoxan may serve as a valid index of 5-HT1A receptor function in humans.
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PMID:Serotonin1A receptor activation by flesinoxan in humans. Body temperature and neuroendocrine responses. 859 27

Recently, our laboratory found a significant enhancing effect of L-5-hydroxy-tryptophan (L-5-HTP) on post-dexamethasone (DST) plasma adrenocorticotropic hormone (ACTH) and cortisol levels in major-but not in minor-depression. To further elucidate the effects of central serotonin (5-HT) activity on the negative feedback of glucocorticoids on hypothalamic-pituitary-adrenal (HPA)-axis function in depression, this study investigates the effects of buspirone, a 5-HT1A receptor agonist, on post-DST ACTH and cortisol levels in 75 depressed subjects. Plasma post-DST ACTH and cortisol concentrations were significantly increased by the acute administration of buspirone (30 mg PO) compared to placebo. There were no differences in buspirone-induced post-DST ACTH or cortisol responses between minor and major depression. There were significant correlations between post-DST ACTH and cortisol, and between post-DST-buspirone ACTH and cortisol. The buspirone-induced post-DST cortisol responses were significantly higher in depressed women than men. It is concluded that buspirone may augment ACTH and, consequently, cortisol escape from suppression by dexamethasone in major as well as in minor depression.
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PMID:Acute administration of buspirone increases the escape of hypothalamic-pituitary-adrenal-axis hormones from suppression by dexamethasone in depression. 877 5

Hypothermic and hormonal responses to a challenge with a selective 5-HT1A receptor agonist ipsapirone are considered to provide an index of 5-HT1A receptor function in humans. To examine the effects of divalproex sodium (DVP) on 5-HT1A receptor function in humans, we measured the hypothermic, adrenocorticotropic hormone (ACTH) cortisol, and behavioral responses to ipsapirone in 10 healthy male volunteers. After obtaining a blood sample for baseline hormone levels and measuring body temperature, a single dose of 0.3 mg/kg of ipsapirone was given orally to all the subjects and further bloods and temperature reading were obtained at regular intervals for three hours. The ipsapirone challenge tests were repeated after the subjects had been treated with DVP (1000 mg/day) for one week. The results showed that the hypothermia induced by ipsapirone was significantly attenuated by the DVP treatment, whereas the ACTH/cortisol release and the behavioral responses following ipsapirone challenges were not altered. Our findings suggest that DVP may enhance 5-HT neurotransmission in humans via a subsensitization of 5-HT1A autoreceptors but does not appear to affect postsynaptic 5-HT1A receptors.
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PMID:Effects of divalproex sodium on 5-HT1A receptor function in healthy human males: hypothermic, hormonal, and behavioral responses to ipsapirone. 939 26

To examine the direct effects of serotonin (5-HT) on the release and synthesis of corticotropin-releasing factor (CRF) in the hypothalamic paraventricular nucleus (PVN), 5-HT was microinjected just onto the bilateral PVN of conscious rats. Plasma adrenocorticotropic hormone (ACTH) levels peaked at 30 min and returned to the basal levels in 90 min. Northern blot analysis revealed that the CRF messenger RNA (mRNA) level in the PVN as well as the proopiomelanocortin mRNA level in the anterior pituitary significantly increased 120 min after the 5-HT injections (50-250 nmol/side). Pretreatment with intracerebroventricular (i.c.v.) injection of pindobind 5-HT1A (5 nmol) or LY-278584 (500 nmol) completely abolished the 5-HT-induced ACTH response, whereas LY-53857 (100 nmol) was without effect. These results suggest that 5-HT stimulates CRF release, which has interactions with 5-HT1A and 5-HT3 receptors on CRF neurons in the PVN, and activates CRF synthesis in conscious rats.
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PMID:Serotonin stimulates corticotropin-releasing factor gene expression in the hypothalamic paraventricular nucleus of conscious rats. 953 2


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