Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies suggest that the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) increases the secretion of oxytocin, adrenocorticotropic hormone (ACTH), corticosterone and prolactin but not renin. However, the lack of selective 5-HT1A receptor antagonists made it difficult to confirm that 5-HT1A receptors mediate the neuroendocrine responses to 8-OH-DPAT. This study investigated the effects of increasing doses of a selective 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide (WAY-100635) on neuroendocrine responses induced by the 5-HT1A receptor agonist 8-OH-DPAT in adult male rats. 8-OH-DPAT, 500 microg/kg s.c., increased plasma levels of oxytocin (to 970% above basal levels); ACTH (to 1622% above basal levels), corticosterone (to 458% above basal levels) and prolactin (to 313% above basal levels), but not renin. The lowest dose of WAY-100635 (0.1 mg/kg s.c.) significantly inhibited the 8-OH-DPAT-induced increase in plasma oxytocin but not ACTH or corticosterone levels. At a dose of 1 mg/kg (s.c.), WAY-100635 completely blocked the oxytocin and ACTH responses and maximally inhibited the corticosterone response to 8-OH-DPAT, although corticosterone levels were still above basal. In contrast, the increase in prolactin secretion, induced by 8-OH-DPAT was not inhibited by any dose of WAY-100635. At the highest dose of WAY-100635 (10 mg/kg, s.c.), basal prolactin levels were markedly elevated (1550%) and administration of 8-OH-DPAT significantly elevated plasma renin concentration. Taken together, these data indicate that: (1) 8-OH-DPAT stimulates oxytocin, ACTH, and corticosterone but not prolactin secretion via activation of 5-HT1A receptors and (2) blockade of 5-HT1A receptors may unmask 8-OH-DPAT simulation of renin secretion via non-5-HT1A receptor mechanisms.
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PMID:WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but not prolactin secretion. 965 68

In the present study, we examined denervation-induced changes in the sensitivity of hypothalamic postsynaptic serotonin1A (5-HT1A) receptor function with respect to changes in the dose-dependent elevation in plasma hormones [adrenocorticotropic hormone (ACTH), corticosterone, prolactin, oxytocin, prolactin, renin and vasopressin] by the 5-HT1A agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT). Rats received intracerebroventricular (i.c.v.) injections of the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or vehicle (0.1% ascorbate in saline) 3 weeks before challenge with increasing doses of 8-OH-DPAT (0, 10, 50 or 200 micrograms/kg s.c.). The effectiveness of 5,7-DHT-induced destruction of serotonergic neurons was confirmed by a 93% reduction in [3H]paroxetine-labeled 5-HT uptake sites in the hypothalamus. No changes in basal levels of ACTH, corticosterone, oxytocin, prolactin, renin and vasopressin were observed in rats that received i.c.v. 5,7-DHT injections. The dose-response curves for 8-OH-DPAT-induced elevations of plasma corticosterone and prolactin levels were shifted to the left in rats treated with 5,7-DHT, whereas no significant difference in the ACTH dose-response curve was observed between rats treated with vehicle and rats treated with 5,7-DHT. In contrast, the maximal oxytocin response to 8-OH-DPAT was attenuated in rats treated with 5,7-DHT. A 5,7-DHT-induced decline in the synthesis of oxytocin could explain this phenomenon. Although 8-OH-DPAT did not increase plasma levels of renin or vasopressin in rats treated with vehicle, 8-OH-DPAT produced an elevation (75%) in plasma renin concentration but not in vasopressin levels in rats that received i.c.v. injections of 5,7-DHT. No change was observed in [3H]8-OH-DPAT labeled 5-HT1A receptors in the hypothalamus. In summary, denervation of hypothalamic serotonergic nerve terminals produces supersensitivity of some neuroendocrine responses to 8-OH-DPAT independent of changes in the density of hypothalamic 5-HT1A receptors.
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PMID:Alterations in 8-hydroxy-2-(dipropylamino)tetralin-induced neuroendocrine responses after 5,7-dihydroxytryptamine-induced denervation of serotonergic neurons. 965 67

Long-term exposure to fluoxetine produces a desensitization of hypothalamic postsynaptic 5-hydroxytryptamine (5-HT)1A receptors, indicated by a substantial inhibition of the 5-HT1A receptor-mediated stimulation of oxytocin and adrenocorticotropic hormone (ACTH) secretion. The present study investigated the time course and mechanism of this desensitization after discontinuation of fluoxetine administration. Male rats were injected with saline or fluoxetine (10 mg/kg/day, i.p.) for 14 days and were challenged with a 5-HT1A agonist, [8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) 50 microg/kg, s.c.] 2, 4, 7, 14, 28, or 60 days post-treatment. In control animals, 8-OH-DPAT significantly increased (approximately 15-fold) plasma levels of oxytocin and ACTH. At 2 days post-treatment, oxytocin and ACTH responses to 8-OH-DPAT were reduced by 74% and 68%, respectively. During further withdrawal from fluoxetine, there was a gradual increase in the oxytocin response toward control levels. However, even 60 days after discontinuation of fluoxetine, the oxytocin response was still significantly reduced by 26% compared with controls. In contrast, the suppressed ACTH response to 8-OH-DPAT (a less-sensitive indicator of desensitization) gradually returned to control levels by day 14 of withdrawal from fluoxetine. Interestingly, the sustained reductions in the hormone responses occurred in the absence of reductions in Gz or Gi protein levels in the hypothalamus. Furthermore, this desensitization was sustained in the absence of detectable levels of fluoxetine and norfluoxetine in plasma and brain tissue. These findings suggest that the sustained desensitization of hypothalamic 5-HT1A receptor systems, observed during fluoxetine withdrawal, may be due to altered interactions among the protein components of the 5-HT1A receptor system, rather than their absolute levels.
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PMID:Sustained desensitization of hypothalamic 5-Hydroxytryptamine1A receptors after discontinuation of fluoxetine: inhibited neuroendocrine responses to 8-hydroxy-2-(Dipropylamino)Tetralin in the absence of changes in Gi/o/z proteins. 991 59

The serotonin receptors involved in the secretion of adrenocorticotropin hormone (ACTH) were investigated in conscious adult male rats. Administration of serotonin (5-HT), 5-hydroxytryptophan (5-HTP) in combination with the serotonin reuptake inhibitor fluoxetine (Flx), or of the 5-HT agonists 8-OH-DPAT (5-HT1A), 5-carboxamido-tryptamine (5-HT1A+1B+5A+7), RU 24969 (5-HT1B+1A), DOI (5-HT2A+2c), S-alpha-methyl-5-HT (5-HT2A+2B+2c), MK212 (5-HT2B+2c), or methyl-chlorophenyl-piperazine (5-HT2A+2c) dose-dependently stimulated ACTH secretion. The 5-HT3 agonist 2-methyl-5-HT had no effect. Administration of a 5-HT1 agonist in combination with any of the 5-HT2 agonists DOI, S-alpha-methyl-5-HT or MK212 had an additive effect on the plasma concentration of ACTH. The ACTH stimulating effect of each of the 5-HT agonists was inhibited by pretreatment with antagonists with corresponding 5-HT receptor affinity. The ACTH response to 5-HT or 5-HTP/Flx was inhibited by injection with the 5-HT1A+2A+2c+5A+7 antagonist methysergide, the 5-HT2A antagonist ketanserine and the 5-HT2C+2A antagonist LY 53857. The 5-HT1A antagonist WAY 100635 enhanced 5-HT- and 5-HTP/Flx-induced ACTH secretion, suggesting a presynaptic 5-HT1A autoreceptor effect of the drug. The 5-HT3 antagonist ondansetrone had no effect on the either of the 5-HT agonists. The 5-HT3+4 antagonist tropisetrone attenuated the effect of 5-HTP/Flx, which may suggest a stimulation of ACTH secretion via 5-HT4 receptors. It is concluded that 5-HT1A, 5-HT2A+2C, and to a lesser extent 5-HT1B receptors, but not 5-HT3 receptors are involved in the effects of serotonin agonists on ACTH secretion. Furthermore, an involvement of the 5-HT5A and the 5-HT7 receptor is possible.
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PMID:Adrenocorticotropic hormone secretion in rats induced by stimulation with serotonergic compounds. hsj@mfi.ku.dk. 1022 82

Although selective 5-hydroxytryptamine (5-HT) reuptake inhibitors (SSRIs) are widely used in the chronic treatment of several anxiety disorders, increased anxiety has been observed in some patients at the beginning of treatment with these compounds. Similar increases in anxiety-related behaviors have been observed in animal studies following a single injection with SSRIs. The mechanism underlying this effect is unclear. The aim of the present study was to investigate the effects of a variety of psychoactive compounds on the anxiogenic-like activity of fluoxetine. The drugs used included the benzodiazepine diazepam, the 5-HT1A receptor partial agonist buspirone, the 5-HT1A receptor antagonists pindolol and WAY-100635, the non-selective 5-HT2 receptor antagonists methiothepin, mianserin and ritanserin, the non-selective dopamine (DA) receptor antagonist haloperidol, the D1 antagonist SCH23390, the selective D2 antagonist raclopride, the D2/3 agonist quinelorane, the cholecystokininB (CCK(B)) receptor antagonist LY 288513, and the corticotropin-releasing factor1 (CRF1) receptor antagonist CP-154,526. Experiments were performed in the free-exploration test. This model is based on the strong neophobic reactions exhibited by BALB/c mice when confronted simultaneously with a familiar and a novel environment. When administered alone, diazepam (1 and 2 mg/kg), buspirone (1 mg/kg) and mianserin (0.3 mg/kg) produced anxiolytic-like effects as they significantly increased exploratory activity of the novel compartment. In contrast, fluoxetine (20 mg/kg) almost completely suppressed exploration of the novel area. Diazepam reversed the anxiogenic-like as well as the locomotor impairment induced by fluoxetine, while quinelorane blocked only the anxiogenic action of fluoxetine. None of the other compounds was able to counteract this effect. Taken together, these results suggest that dopaminergic mechanisms may underlie, at least in part, the behavioral effects of fluoxetine in the free-exploration test, whereas 5-HT1A 5-HT2, CCK(B) and CRF1 receptors may not be involved primarily in these effects.
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PMID:An investigation of the mechanisms responsible for acute fluoxetine-induced anxiogenic-like effects in mice. 1148 52

We previously reported the presence of serotonin (5-HT) in testes from golden hamster, a photoperiodic species which is a useful model for the study of states of male (in)fertility. The aims of this study were to investigate: (1) the presence of intrinsic sources of 5-HT in the testis; (2) the role of 5-HT in in vitro androgen production; (3) the serotoninergic receptor subtypes in the testis, and (4) the existence of interactions among the 5-HT receptors and the testicular catecholaminergic and corticotropin-releasing hormone (CRH) systems. Immunohistochemical studies revealed the presence of tryptophan hydroxylase, a 5-HT-biosynthetic enzyme, in interstitial cells which show the characteristic punctate chromatin pattern of Leydig cells. We describe an inhibitory action of 5-HT on testosterone, dihydrotestosterone, and androstane-3alpha,17beta-diol production from testes of peripubertal and adult hamsters maintained in a long photoperiod (14/10 h light/dark), and adult animals exposed to a short photoperiod (6/18 h light/dark). By using several agonists and antagonists of 5-HT receptors, we characterized 5-HT1A and 5-HT2A receptor subtypes involved in the inhibitory action of this neurotransmitter on human chorionic gonadotropin stimulated cyclic adenosine monophosphate and testosterone production. CRH also produced a negative modulation of both parameters, but epinephrine and norepinephrine, through alpha1/beta1-adrenergic receptors, exerted a stimulatory action. 5-HT1A, 5-HT2, and CRH antagonists showed that the testicular activity of the serotoninergic system, but also the alpha1/beta1-adrenergic receptor system, is mediated by CRH. Moreover, interactions between the 5-HT2A receptor system and alpha1/beta-adrenergic receptors have been established. Thus, these data suggest that alpha1/beta1-adrenergic receptors are involved in the local regulatory action exerted by 5-HT on steroidogenesis through a 5-HT2-receptor-mediated response and the CRH system.
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PMID:Interactions between testicular serotoninergic, catecholaminergic, and corticotropin-releasing hormone systems modulating cAMP and testosterone production in the golden hamster. 1209 15

The neurotransmitter serotonin (5-HT) stimulates adrenocorticotropic hormone (ACTH) secretion from the anterior pituitary gland via activation of central 5-HT1 and 5-HT2 receptors. The effect of 5-HT is predominantly indirect and may be mediated via release of hypothalamic corticotropin-releasing hormone (CRH). We therefore investigated the possible involvement of CRH in the serotonergic stimulation of ACTH secretion in male rats. Increased neuronal 5-HT content induced by systemic administration of the precursor 5-hydroxytryptophan (5-HTP) in combination with the 5-HT reuptake inhibitor fluoxetine raised CRH mRNA expression in the paraventricular nucleus (PVN) by 64%, increased pro-opiomelanocortin (POMC) mRNA in the anterior pituitary lobe by 17% and stimulated ACTH secretion five-fold. Central administration of 5-HT agonists specific to 5-HT1A, 5-HT1B, 5-HT2A or 5-HT2C receptors increased CRH mRNA in the PVN by 15-50%, POMC mRNA in the anterior pituitary by 15-27% and ACTH secretion three- to five-fold, whereas a specific 5-HT3 agonist had no effect. Systemic administration of a specific anti-CRH antiserum inhibited the ACTH response to 5-HTP and fluoxetine and prevented the 5-HTP and fluoxetine-induced POMC mRNA response in the anterior pituitary lobe. Central or systemic infusion of 5-HT increased ACTH secretion seven- and eight-fold, respectively. Systemic pretreatment with the anti-CRH antiserum reduced the ACTH responses to 5-HT by 80% and 64%, respectively. It is concluded that 5-HT via activation of 5-HT1A, 5-HT2A, 5-HT2C and possibly also 5-HT1B receptors increases the synthesis of CRH in the PVN and POMC in the anterior pituitary lobe, which results in increased ACTH secretion. Furthermore, the results indicate that CRH is an important mediator of the ACTH response to 5-HT.
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PMID:Serotonergic stimulation of corticotropin-releasing hormone and pro-opiomelanocortin gene expression. 1237 3

The neurotransmitter serotonin (5-HT) stimulates the secretion of vasopressin and oxytocin, and 5-HT is involved in the mediation of the vasopressin and oxytocin response to stress. In male Wistar rats, we investigated the 5-HT receptors involved in the 5-HT-induced increase of mRNA expression of vasopressin and oxytocin in the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The 5-HT precursor, 5-hydroxytryptophan, injected in combination with the 5-HT reuptake inhibitor, fluoxetine, increased oxytocin mRNA expression in the PVN, and the concentration of vasopressin and oxytocin in plasma, whereas mRNA in the SON was not affected. Intracerebroventricular infusion of 5-HT agonists selective for the 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptor increased oxytocin mRNA in the SON and PVN. Infusion of agonists selective for the 5-HT2A + 2C receptor increased vasopressin mRNA in the PVN, whereas none of the 5-HT agonists affected vasopressin mRNA in the SON. All the 5-HT agonists infused increased peripheral oxytocin concentration and vasopressin was increased by stimulation of the 5-HT2A, 5-HT2C and 5-HT3 receptor. Intracerebroventricular infusion of 100 nmol 5-HT increased the extracellular hypothalamic concentration of vasopressin as measured by microdialysis in the PVN. To evaluate the involvement of hypothalamic-pituitary system in the 5-hydroxytryptophan and fluoxetine-induced vasopressin secretion, rats were immunoneutralized with a specific anti-corticotropin-releasing hormone antiserum. This treatment reduced plasma vasopressin and oxytocin responses. We conclude that stimulation with 5-hydroxytryptophan or 5-HT agonists increases mRNA expression of oxytocin in the PVN and the SON via stimulation of at least 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptors. Vasopressin mRNA in the PVN was increased only via the 5-HT2 receptor, whereas vasopressin mRNA in the SON does not seem to be affected by 5-HT stimulation. Corticotropin-releasing hormone appears to be partly involved in the mediation of 5-HT induced vasopressin and oxytocin secretion.
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PMID:Serotonin stimulates hypothalamic mRNA expression and local release of neurohypophysial peptides. 1271 7

Serotonin (5-hydroxytryptamine, 5-HT)-containing neurons in the midbrain directly innervate corticotropin-releasing hormone (CRH)-containing cells located in paraventricular nucleus of the hypothalamus. Serotonergic inputs into the paraventricular nucleus mediate the release of CRH, leading to the release of adrenocorticotropin, which triggers glucocorticoid secretion from the adrenal cortex. 5-HT1A and 5-HT2A receptors are the main receptors mediating the serotonergic stimulation of the hypothalamic-pituitary-adrenal axis. In turn, both CRH and glucocorticoids have multiple and complex effects on the serotonergic neurons. Therefore, these two systems are interwoven and communicate closely. The intimate relationship between serotonin and the hypothalamic-pituitary-adrenal axis is of great importance in normal physiology such as circadian rhythm and stress, as well as pathophysiological disorders such as depression, anxiety, eating disorders, and chronic fatigue.
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PMID:Serotonin and the neuroendocrine regulation of the hypothalamic--pituitary-adrenal axis in health and disease. 1285 56

3,4-methylenedioxy-N-methylamphetamine (MDMA, 'Ecstasy') is a potent inhibitor of serotonin uptake, which induces both an increase in locomotion and a decrease in exploratory activity in rodents. Serotonin 5-HT1B receptors, located on the terminals of striatal efferent neurons, have been suggested to mediate these motor effects of MDMA. Striatal neurons projecting to the globus pallidus contain met-enkephalin, whilst those projecting to the substantia nigra contain substance P. We therefore analysed the levels of both peptides using radioimmunocytochemistry after MDMA administration (10 mg/kg, 3 h) in wild-type and 5-HT1B receptor knockout mice. Our results demonstrate that MDMA induces a decrease in pallidal met-enkephalin immunolabelling in wild-type, but not in 5-HT1B receptor knockout mice. Similar results were obtained following treatment with the 5-HT1A/1B agonist RU24969 (5 mg/kg, 3 h), suggesting that activation of 5-HT1B receptors leads to a reduction in met-enkephalin levels in the globus pallidus. In contrast, MDMA had no effect on the nigral substance P levels. We have previously shown that both MDMA and RU24969 fail to stimulate locomotor activity in 5-HT1B receptor knockout mice. Our present data indicate that the opioid antagonist naloxone suppressed the locomotor effects of MDMA. This study is the first to demonstrate that Enk contributes to MDMA-induced increases in locomotor activity. Such an effect may be related to the 5-HT control of pallidal met-enkephalin levels via the 5-HT1B receptors.
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PMID:Enkephalin contributes to the locomotor stimulating effects of 3,4-methylenedioxy-N-methylamphetamine. 1288 20


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