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)

Experiments were performed with slices of rat hippocampus in order to investigate whether the release of acetylcholine in this area is modulated through 5-hydroxytryptamine (5-HT) receptors. The slices were prelabeled with [3H]choline then stimulated electrically twice for 4 min each at a frequency of 3 Hz. The overflow of tritium evoked was inhibited by exogenous 5-HT in a concentration-dependent manner. The 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HC1 ((+/-)-DOI), did not mimic 5-HT. The effect of 5-HT was antagonized by methiothepin but not by the 5-HT2 antagonist, ketanserin. The 5-HT1 agonist, 5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole (RU 24969), inhibited the electrically evoked overflow of tritium, whereas the 5-HT1A-selective agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), was ineffective. Methiothepin itself, but not ketanserin, increased the evoked overflow of tritium. In contrast, the overflow was inhibited by the 5-HT uptake blocker, 6-nitroquipazine. The evoked overflow was also reduced by d-fenfluramine, a serotonin releaser. The concentration-inhibition curve for d-fenfluramine was shifted to the right by methiothepin. It is concluded that the release of ACh in rat hippocampus may be tonically inhibited by 5-HT through the activation of receptors, possibly belonging to the 5-HT1B subtype.
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PMID:Acetylcholine release from rat hippocampal slices is modulated by 5-hydroxytryptamine. 252 65

1. 5-Hydroxytryptamine (5-HT) plays a role in the regulation of noradrenergic neurones in the brain, but the precise mechanism of regulation of noradrenaline (NA) release by 5-HT1A receptors has not been defined. The present study describes the effect of a highly potent and selective 5-HT1A receptor agonist, 5-(3-[[(2S)-1,4-benzodioxan-2-ylmethyl)]amino]propoxy)-1,3-b enzodioxole HC1 (MKC-242), on NA release in the hypothalamus using microdialysis in the freely moving rat. 2. Subcutaneous injection of MKC-242 (0.5 mg kg-1) increased extracellular levels of NA and its metabolite, 3-methoxy-4-hydroxyphenylglycol, in the hypothalamus and hippocampus. 3. The 5-HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.2 mg kg-1) and buspirone (3 mg kg-1) mimicked the effect of MKC-242 in increasing NA release in the hypothalamus. 4. The effects of MKC-242 and 8-OH-DPAT in the hypothalamus were antagonized by pretreatment with WAY100135 (10 mg kg-1), a silent 5-HT1A receptor antagonist. 5. Local administration of 8-OH-DPAT (10-100 microM), citalopram (1 microM), a 5-HT reuptake inhibitor, and MDL72222 (10 microM), a 5-HT3 receptor antagonist, into the hypothalamus, had no effect on NA release. 6. Intracerebroventricular injection with 5,7-dihydroxytryptamine caused a marked reduction in brain 5-HT content, but the treatment affected neither basal NA levels nor the MKC-242-induced increase in NA release. 7. The effect of MKC-242 in increasing NA release was not attenuated by repeated treatment with the drug (0.5 mg kg-1, once a day for 2 weeks). 8. The present results suggest that activation of postsynaptic 5-HT1A receptors increases NA release in the hypothalamus.
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PMID:Increase of noradrenaline release in the hypothalamus of freely moving rat by postsynaptic 5-hydroxytryptamine1A receptor activation. 758 94

The present study characterized the serotonin (5-HT) receptor subtypes mediating adrenal corticotropic hormone (ACTH) and corticosterone responses to 5-HT agonists in conscious rats. The 5-HT2A/5-HT2C agonist (+/-(-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HC1 (DOI) increased plasma ACTH and corticosterone in a dose-dependent manner. The 5-HT2A/5-HT2C antagonist ritanserin (0.01 and 0.1 mg/kg sc) inhibited the DOI-induced increase in plasma ACTH, but not corticosterone. Low doses of spiperone (0.01 and 0.1 mg/kg sc) significantly reduced the ACTH response to DOI. Because spiperone has a higher affinity for 5-HT2A than 5-HT2C receptors, these data suggest that DOI stimulates ACTH secretion through 5-HT2A receptors. 5-methoxy-3-[1,2,3,4-tetrahydro-4-pyridinyl]-1H-indole (RU 24969) is a potent 5-HT1A/1B and moderate 5-HT2C agonist that also has been suggested to release 5-HT. However, p-chlorophenylalanine (PCPA) did not reduce the effect of RU 24969 on plasma ACTH, suggesting that RU 24969 only acts as a direct agonist. 6-methyl-1-[1-methylethyl]ergoline-8-carboxylic acid (LY53857) injected into the lateral cerebral ventricles (i.c.v.) inhibited the ACTH, but not corticosterone response to peripheral injection of RU 24969, suggesting that central 5-HT2A/2C receptors mediate the ACTH response. LY53857 injection (i.c.v.) also inhibited the effect of p-chloroamphetamine (i.c.v.) on plasma ACTH. However, the corticosterone response was not inhibited by LY53857, suggesting a distinct location of 5-HT receptors regulating corticosterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence that ACTH secretion is regulated by serotonin2A/2C (5-HT2A/2C) receptors. 799 80

Effects of MKC-242 (5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-b enzodioxole HC1), a novel 5-HT1A-receptor agonist, and reference compounds on wrap restraint stress-induced defecation were evaluated in rats. Wrapping restraint stress increased defecation in rats. The increase was attenuated by putative 5-HT1A-receptor agonists, MKC-242 and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The suppressive effect of MKC-242 on wrap stress-induced defecation was antagonized by prior administration of a 5-HT1A-receptor antagonist, WAY100135. MKC-242 did not affect spontaneous defecation and 5-HT-induced defecation. Diazepam and amitriptyline also significantly reduced the stress-induced defecation. However, amitriptyline showed a potent anti-cholinergic effect in the oxotremorine-induced tremor test and reduced spontaneous defecation. In contrast to MKC-242 and 8-OH-DPAT, buspirone and tandospirone tended to suppress the increase at high doses. A major metabolite of buspirone and tandospirone, 1-(2-pyrimidinyl)piperazine, antagonized the suppressive effect of MKC-242. These findings suggest that stimulation of 5-HT1A receptors reduces stress-induced defecation but not spontaneous and 5-HT-induced defecation and that MKC-242 may be useful for the treatment of irritable bowel syndrome.
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PMID:Reduction of wrap restraint stress-induced defecation by MKC-242, a novel benzodioxan derivative, via 5-HT1A-receptor agonist action in rats. 971 68