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)

8-OH-DPAT, a selective 5-HT1A agonist, produced a hypothermic response in mice at a dosage of 0.5 mg/kg. Administration of corticosterone-21-acetate (0.5, 5 and 50 mg/kg, daily for 3 and 10 days) produced a dose-dependent attenuation of this hypothermic response in mice. When all controls and corticosterone treated mice were retested, 14 days after initial testing, they did not differ in the hypothermic responses induced by 8-OH-DPAT. Mice treated with aldosterone (50 mg/kg), dexamethasone (50 mg/kg) and the specific type 2 corticosteroid receptor agonist, 11b,17b-dihydroxy-21-methyl-17a-pregna-1,4,6-trien-20-yn+ ++-3-one (RU26988, 30 mg/kg) for 10 days, did not differ from vehicle treated controls in the hypothermic response to 8-OH-DPAT. Mice administered corticosterone-21-acetate (30 mg/kg, daily) for 10 days displayed a motor behavioural syndrome, which was not seen in controls, when injected with 5-hydroxytryptophan (5-HTP, 100 mg/kg) 15 min after the injection of carbidopa (25 mg/kg). This was significantly decreased by pretreatment with the 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)-piperazine (NAN-190 5 mg/kg, 30 min prior to administration of carbidopa). Taken together, this evidence is compatible with a specific corticosterone induced facilitation of 5-HT release due to attenuation of inhibitory 5-HT1A autoreceptor function.
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PMID:Effects of glucocorticoids on 5-HT1A presynaptic function in the mouse. 783 29

We recently reported that chronic administration of the 5-HT1A receptor agonist, ipsapirone (0.5 milligrams in drinking water for 3 weeks), has anxiolytic activity in the rat. Herein, we investigated whether this treatment promotes tachyphylaxis to the acute neuroendocrine effects of ipsapirone. Rats chronically treated with ipsapirone displayed a 7% decrease in body weights, compared to vehicle-pretreated rats, thereby confirming previous observations. On the other hand, ipsapirone pretreatment did not affect basal plasma levels of adrenocorticotropin (ACTH), corticosterone, prolactin, aldosterone, and renin activity, nor did it affect their respective rises following an acute ipsapirone (50 mg/kg PO) challenge. Moreover, ipsapirone pretreatment did not affect the increase in plasma prolactin levels elicited by the dopaminergic receptor antagonist haloperidol. These results suggest that neither the 5-HT1A receptors nor the catecholamine receptors that mediate ipsapirone acute neuroendocrine effects develop tolerance to stimulation upon sustained ipsapirone treatment.
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PMID:Chronic treatment with an anxiolytic dose of the 5-HT1A agonist ipsapirone does not alter ipsapirone acute neuroendocrine effects. 790 66

We evaluated the effects of adrenalectomy (ADX) and replacement with glucocorticoid receptor agonists on serotonin (5-HT) 5-HT1A and 5-HT2 receptor binding in rat brain. 5-HT1A receptor binding was increased in the CA2-CA4 and the dentate gyrus of the hippocampus 1 week after ADX. This effect was prevented by the systemic administration of aldosterone (10 micrograms/microliters/h) but not by RU28362 (10 micrograms/microliters/h). No significant effect was observed on 5-HT2 receptor binding in rat cortex. The expression of 5-HT transporter mRNA was unchanged in the raphe nucleus as measured by in situ hybridization.
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PMID:Effects of adrenalectomy and type I or type II glucocorticoid receptor activation on 5-HT1A and 5-HT2 receptor binding and 5-HT transporter mRNA expression in rat brain. 792 18

In the rat brain, the dorsal raphe nucleus contains a large proportion of serotoninergic neurons, which are mostly regulated by somato-dendritic 5-HT1A autoreceptors. This nucleus also possesses intracellular glucocorticoid receptors (GR), which may be involved in the well established modulation of serotonin (5-hydroxytryptamine, 5-HT) metabolism by glucocorticoids. Control by corticosteroids of 5-HT1A receptor-mediated inhibitory control of the firing of serotoninergic neurons in the dorsal raphe nucleus was investigated using an in vitro electrophysiological approach. The spontaneous firing rate of serotoninergic neurons recorded in brain stem slices and its inhibition due to 5-HT1A autoreceptor stimulation by 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) were similar in adrenalectomized rats and sham-operated animals. In vitro pretreatment with corticosterone (30-100 nM) significantly reduced 8-OH-DPAT-induced inhibition of the 5-HT cell discharge in slices from adrenalectomized rats. This effect could be prevented by the GR antagonist, 11 beta-(4-dimethyl-amino-phenyl)- 17 beta-hydroxy-17 alpha-(prop-1-ynyl)estra-4,9-dien-3-one (RU) 38486, 30 nM), and mimicked by the GR agonist, 11 beta, 17 beta-dihydroxy-6-methyl-17 alpha (prop-1-ynyl) androsta-1,4,6-trien-3-one (RU 28362, 500 nM). In contrast, the mineralocorticoid receptor (MR) agonist, aldosterone (10 nM), did not alter 8-OH-DPAT-induced inhibition in tissues from adrenalectomized animals. Complementary autoradiographic experiments showed that [3H]8-OH-DPAT specific binding to 5-HT1A sites in the dorsal raphe nucleus (and the hippocampus) was not significantly altered following adrenalectomy and exposure of brain stem slices to corticosterone. These data suggest that GR are involved in the suppressive effects of high levels of corticosterone on the 5-HT1A receptor-dependent regulation of 5-HT neuronal activity in the rat dorsal raphe nucleus.
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PMID:Glucocorticoid receptor-mediated inhibition by corticosterone of 5-HT1A autoreceptor functioning in the rat dorsal raphe nucleus. 853 91

Serotonin (5-HT) has been shown to modulate brain maturation during development and adult plasticity. This effect in the whole animal may be due to activation of 5-HT1A receptors and a corresponding increases in S100b and corticosterone. Synaptophysin, an integral protein of the synaptic vesicle membrane that correlates with synaptic density and neurotransmitter release, is reduced by depletion of 5-HT in the cortex and hippocampus of the adult rat. Injections of a 5-HT1A agonist or dexamethasone can reverse the loss of synaptophysin immunoreactivity (IR). In this study we used morphometric analysis of synaptophysin-IR to study the effects of the 5-HT1A agonist, ipsapirone, and the neuronal extension factor, S100b on hippocampal neurons grown in a serum and steroid free media. Both compounds increased the synaptophysin-IR at doses previously established to be highly specific. Ipsapirone (10(-9)M) was more effective on neuronal cell bodies staining and S100b (10 ng/ml) was more effective in increasing the number of synaptophysin-IR varicosities on neuronal processes. In addition both types of corticosteroid receptor agonists, at previously established specific doses, Ru28362 (10(-8) M) and aldosterone (10(-9) M) produced smaller increases compared to control groups in both the cell body staining and the number of varicosities. The effect of these differentiating factors on the expression of synaptophysin-IR suggests multiple regulation sites for producing and maintaining pre-synaptic elements in the brain.
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PMID:Enhanced synaptophysin immunoreactivity in rat hippocampal culture by 5-HT 1A agonist, S100b, and corticosteroid receptor agonists. 872 30

The effects of corticosteroid receptor agonists on the expression of 5-HT1A receptor mRNA were measured in rat hippocampal cultures using in situ hybridization histochemistry. In our normal culture system, grown in serum and steroid-free media, moderate to heavy signal for 5-HT1A mRNA transcripts were detected in hippocampal neurons and glial cells. Aldosterone, a type I corticosteroid receptor agonist (10(-9) M), significantly reduced the expression of 5-HT1A mRNA both in neurons and glial fibrillary acidic protein (GFAP)-immunoreactive (IR) cells. The type II corticosteroid receptor agonist, Ru28362 (10(-8) M), also significantly decreased neuronal 5-HT1A mRNA expression. However, it was not as effective as aldosterone in reducing the label over GFAP-IR cells. These data indicate that corticosteroids may directly regulate the expression of hippocampal 5-HT1A receptors at the mRNA level in cultured hippocampal cells.
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PMID:5-HT1A receptor expression is modulated by corticosteroid receptor agonists in primary rat hippocampal culture. 881 66

Corticosteroids influence neuron activity in the hippocampus through the activation of mineralocorticoid and glucocorticoid receptors. For example, corticosteroids modulate the responses elicited by the activation of several different neurotransmitter receptors on hippocampal pyramidal cells. However, the effects of corticosteroids on the serotonin (5-HT) receptors systems in subfield CA3 are not completely known. Therefore, we used single-electrode voltage clamp techniques to examine the actions of chronic corticosteroid treatment on the 5-HT1A receptor-effector pathway in rat hippocampal subfield CA3 pyramidal cells. Activation of the 5-HT1A receptor increases the conductance of an inward rectifying potassium channel, increasing outward current. The treatment groups used in this investigation were: adrenalectomy, selective mineralcorticoid receptor activation with aldosterone, mineralcorticoid receptor and glucocorticoid receptor activation with high levels of corticosterone and SHAM. Corticosteroids altered the characteristics of the 5-HT concentration-response curve for the 5-HT1A receptor. The effective concentration at 50% of maximum value was smaller in cells from the adrenalectomy treatment group compared to the other treatment groups. The maximum response was smaller in cells from the high corticosterone treatment group compared to SHAM and adrenalectomy treatment group animals. G protein function was also altered by corticosterone treatment. Less current was elicited by guanosine 5'-0-13-thiotriphosphate in cells from the high corticosterone treatment group compared to the other treatment groups and in cells from the SHAM treatment group compared to adrenalectomy treatment group animals. Corticosteroid treatment did not alter the current-voltage relationship, the conductance or the reversal potential of the potassium current linked to the 5-HT1A receptor. We conclude that corticosteroids alter the 5-HT1A receptor-mediated-response in hippocampal subfield CA3 neurons at site(s) downstream of the receptor.
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PMID:Corticosteroids alter 5-hydroxytryptamine1A receptor-effector pathway in hippocampal subfield CA3 pyramidal cells. 949 87

Serotonin (5-HT) plays a pivotal role in the regulation of the brain-pituitary-adrenal axis. In particular, 5-HT has been shown to control the activity of hypothalamic CRF neurons and pituitary corticotrope cells through activation of 5-HT1A and (or) 5-HT(2A/2C) receptor subtypes. 5-HT, acting through 5-HT2 receptors, can also trigger the renin-angiotensin system by stimulating renin secretion and consequently can enhance aldosterone production. At the adrenal level, 5-HT produced locally stimulates the secretory activity of adrenocortical cells through a paracrine mode of communication. The presence of 5-HT in the adrenal gland has been demonstrated immunohistochemically and biochemically in various species. In the frog, rat, and pig adrenal gland, 5-HT is synthesized by chromaffin cells, while in the mouse adrenal cortex, 5-HT is contained in nerve fibers. In man, 5-HT is present in perivascular mast cells. In vivo and in vitro studies have shown that 5-HT stimulates corticosteroid secretion in various species (including human). The type of receptor involved in the mechanism of action of 5-HT differs between the various species. In frogs and humans, the stimulatory effect of 5-HT on adrenocortical cells is mediated through a 5-HT4 receptor subtype positively coupled to adenylyl cyclase and calcium influx. In the rat, the effect of 5-HT on aldosterone secretion is mediated via activation of 5-HT7 receptors. Clinical studies indicate that 5-HT4 receptor agonists stimulate aldosterone secretion in healthy volunteers and in patients with corticotropic insufficiency and primary hyperaldosteronism. Local serotonergic control of corticosteroid production may be involved in the physiological control of the activity of the adrenal cortex as well as in the pathophysiology of cortisol and aldosterone disorders.
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PMID:Role of 5-HT in the regulation of the brain-pituitary-adrenal axis: effects of 5-HT on adrenocortical cells. 1114 86