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)

It has been suggested that the late hypotensive response to serotonin (5-hydroxytryptamine; 5-HT) in vagosympathectomised cats, being potently mimicked by 5-carboxamidotryptamine (5-CT), not modified by ketanserin and blocked by methiothepin or methysergide, is mediated by '5-HT1-like' receptors. Nevertheless, current guidelines for 5-HT receptor classification refer to this receptor as an orphan receptor. Thus, the present study set out to reanalyse the above suggestion in terms of the classification schemes proposed in 1994 and 1998 by the NC-IUPHAR subcommittee on the classification of 5-HT receptors. Intravenous (i.v.) bolus injections of 5-CT (0.003-0.3 microg/kg), 5-HT (1-100 microg/kg) and 5-methoxytryptamine (5-MeO-T; 1-100 microg/kg) produced dose-dependent vasodepressor responses with a rank order of agonist potency of 5-CT >> 5-HT = 5-MeO-T with sumatriptan (10-300 microg/kg) virtually inactive. The vasodepressor responses to 5-HT, 5-CT and 5-MeO-T were not attenuated following i.v. administration of the antagonists GR127935 (5-HT(IB/ID); 30 microg/kg), tropisetron (5-HT3/4; 3000 microg/kg), (+/-)-pindolol (beta-adrenergic and 5-HT1A; 4000 microg/kg) or equivalent volumes of physiological saline. In contrast, the above vasodepressor responses were markedly and specifically antagonised by i.v. methiothepin (100 microg/kg), lisuride (30 microg/kg and 100 microg/kg), mesulergine (300 microg/kg and 1000 microg/kg) or LY215840 (300 microg/kg and 1000 microg/kg). The above lines of evidence, therefore, indicate that the orphan receptors mediating the vasodepressor responses to 5-HT in vagosympathectomised cats are pharmacologically similar to other 5-HT7 receptors mediating vascular and non-vascular responses (e.g. relaxation of the canine external carotid artery and guinea-pig ileum as well as feline tachycardia).
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PMID:Further pharmacological analysis of the orphan 5-HT receptors mediating feline vasodepressor responses: close resemblance to the 5-HT7, receptor. 1088 42

Serotonin (5-hydroxytryptamine, 5-HT) has been shown to play a role in immunoregulation; however, little is known about specific subtypes of 5-HT receptors involved in peripheral immunomodulation. In the present study we used RT-PCR methods to examine the mRNA expression of 5-HT receptors in the cells of lymphoid tissues of the rat. All 13 rat 5-HT receptor genes cloned so far were examined in ex vivo isolated spleen, thymus, and peripheral blood lymphocytes, as well as in mitogen-stimulated spleen cells. Positive signals were obtained for 5-HT1B, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT6, and 5-HT7 receptor mRNAs in all three compartments. Mitogen (ConA and PWM) stimulated cells additionally expressed mRNA corresponding to the 5HT-3 receptor subtype. In contrast, 5-HT1A, 5-HT1D, 5-HT2C, 5-HT4, 5-HT5A, and 5-HT5B mRNAs were not detected in any of the examined cell populations. These results may be useful as a starting point for future functional studies on immunomodulatory effects of 5-HT and may help to understand conflicting serotonergic effects on immune functions as found in the literature.
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PMID:mRNA expression of serotonin receptors in cells of the immune tissues of the rat. 1097 Jun 81

Various classes of compounds exist to lower intraocular pressure (IOP) in the treatment of glaucoma. None of them is ideal since some patients respond better than others and the side effects vary between individuals. New classes of compounds need to be introduced to allow the clinician greater scope for effective treatment of all patients. It is now generally agreed that the cause of ganglion cell dysfunction in glaucoma is likely to be multifactorial and that concentrating solely on reducing IOP is inadequate. Irrespective of the reason for the dysfunction, the future goal must be to attenuate cell death. This may be achieved with drugs that interact with components of the retina, and is termed 'neuroprotection'. Thus, drugs that can both reduce IOP and act as neuroprotectants would be ideal for the treatment of glaucoma. In this article we summarise studies on animals which show serotonergic 5-HT1A agonists to both reduce IOP when topically applied to the rabbit eye and blunt the damaging effect to the rat retina and ganglion cells induced by glutamate toxicity or ischaemia. Reduction of IOP occurs via stimulation of 5-HT1A receptors associated with the ciliary processes. Neuroprotection of retinal neurones appears to involve the interaction of 5-HT1A agonists with membrane sodium channels and/or 5-HT1A or even possibly 5-HT7 receptors. Various 5-HT1A agonists are used in patients to treat depression, so classes of these drugs have a proven safety profile for use in patients. The animal studies summarised in this article suggest that 5-HT1A agonists need to be considered as a new class of drugs for the treatment of glaucoma.
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PMID:5-Hydroxytryptamine1A agonists: potential use in glaucoma. Evidence from animal studies. 1102 74

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

The affinity of clozapine for 5-HT2A, 5-HT2C, 5-HT6, 5-HT7, and 5-HT1A receptors has been suggested to contribute to various aspects of its complex clinical actions. This study examined the hypothesis that genetic variation in 5-HT1A, 5-HT6, and 5-HT7 receptor genes is involved in the variability observed in response to clozapine. We employed a pharmacogenetic approach in a group (n=185) of schizophrenia patients that have been clinically well characterized for clozapine response. Polymorphisms in the 5-HT6 (HTR6), 5-HT1A (HTR1A) and 5-HT7 (HTR7) receptor genes were genotyped. No evidence for either an allelic or genotypic association of the T-->C 267 HTR6 polymorphism with response to clozapine was found in our sample (allele: chi(2)=0.06, 1 df, P=0.80; genotype: chi(2)=1.21, 2 df, P=0.55). The pro16leu HTR1A polymorphism was not observed in our sample; all individuals genotyped were pro/pro 16 homozygotes. With respect to the pro279leu HTR7 polymorphism, one Caucasian male responder to clozapine was observed to be heterozygous (pro/leu 279 genotype). This individual was clinically similar to the other clozapine responders. Overall, our findings do not support a role for the T-->C 267 polymorphism of the 5-HT6 receptor gene in response to clozapine, although replication is required to confirm this finding.
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PMID:Lack of association between the T-->C 267 serotonin 5-HT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia. 1116 44

Serotonin (5-HT) and 5-HT receptor agonists can modify the response of the mammalian suprachiasmatic nucleus (SCN) to light. It remains uncertain which 5-HT receptor subtypes mediate these effects. The effects of 5-HT receptor activation on optic nerve-mediated input to SCN neurons were examined using whole-cell patch-clamp recordings in horizontal slices of ventral hypothalamus from the male mouse. The hypothesis that 5-HT reduces the effect of retinohypothalamic tract (RHT) input to the SCN by acting at 5-HT1B receptors was tested first. As previously described in the hamster, a mixed 5-HT(1A/1B) receptor agonist, 1-[3-(trifluoromethyl)phenyl]-piperazine hydrochloride (TFMPP), reduced the amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) evoked by selectively stimulating the optic nerve of wild-type mice. The agonist was negligibly effective in a 5-HT1B receptor knockout mouse, suggesting minimal contribution of 5-HT1A receptors to the TFMPP-induced reduction in the amplitude of the optic nerve-evoked EPSC. We next tested the hypothesis that 5-HT also reduces RHT input to the SCN via activation of 5-HT7 receptors. The mixed 5-HT(1A/7) receptor agonist, R(+)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT), reduced the evoked EPSC amplitude in both wild-type and 5-HT1B receptor knockout mice. This effect of 8-OH-DPAT was minimally attenuated by the selective 5-HT1A receptor antagonist WAY 100635 but was reversibly and significantly reduced in the presence of ritanserin, a mixed 5-HT(2/7) receptor antagonist. Taken together with the authors' previous ultrastructural studies of 5-HT1B receptors in the mouse SCN, these results indicate that in the mouse, 5-HT reduces RHT input to the SCN by acting at 5-HT1B receptors located on RHT terminals. Moreover, activation of 5-HT7 receptors in the mouse SCN, but not 5-HT1A receptors, also results in a reduction in the amplitude of the optic nerve-evoked EPSC. The findings indicate that 5-HT may modulate RHT glutamatergic input to the SCN through 2 or more 5-HT receptors. The likely mechanism of altered RHT glutamatergic input to SCN neurons is an alteration of photic effects on the SCN circadian oscillator.
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PMID:Serotonergic modulation of retinal input to the mouse suprachiasmatic nucleus mediated by 5-HT1B and 5-HT7 receptors. 1122 Jul 75

A new series of 3,4-dihydro-3-amino-2H-1-benzopyran derivatives (1 and 2) bearing various substituents on the 5-position was successfully prepared via palladium-mediated cross-coupling reactions. Some of the new compounds showed high affinity for 5-HT1A and 5-HT7 receptors. The best affinity for the 5-HT1A and 5-HT7 receptors was obtained for 2b (Ki = 0.3 nM for 5-HT1A and 3.1 nM for 5-HT7). The anxiolytic activity of compound 2b was evaluated.
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PMID:5-substituted 3,4-dihydro-3-amino-2H-1-benzopyran derivatives: synthesis and interaction with serotoninergic receptors. 1148 May 47

The substituted amphetamine drugs, 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy') and fenfluramine, are known to damage 5-HT neurons in the brain of animals. However, little is known about the drugs' effects on circadian rhythmicity which is known to be influenced by serotonergic input to the suprachiasmatic nuclei. In the present study, we tested the ability of MDMA and fenfluramine treatment to alter the ability of the circadian clock to reset in response to an agonist of the 5-HT1A and 5-HT7 receptor subtypes soon after treatment with the drugs, and then again at 20 weeks. Coronal hypothalamic slices containing the suprachiasmatic nuclei (SCN) were prepared from rats and 3-min recordings of the firing rate of individual cells were performed throughout a 12-h period. The ability of the 5-HT agonist, 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT), to cause a phase advance in the firing pattern of SCN neurons was assessed in slices from control animals and those pretreated with MDMA or fenfluramine (10, 15 and 20 mg/kg administered on successive days) 6-10 days or 20 weeks previously. Phase advances to 8-OH-DPAT in the slice were attenuated by pretreatment with MDMA or fenfluramine at both drug-test intervals. Our study demonstrates that repeated exposure to MDMA or fenfluramine may interfere with the ability of serotonin to phase shift the circadian clock in the rat. It is possible that such an effect may be responsible for some of the clinical changes, such as sleep disorders and mood changes, sometimes reported by human users of the substituted amphetamines.
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PMID:MDMA and fenfluramine alter the response of the circadian clock to a serotonin agonist in vitro. 1171 26

Steroid hormones synthesized in the brain, called 'neurosteroids', modulate neuronal activity. We treated neonatal rats with a main precursor of the neurosteroidogenesis, pregnenolone, and examined adenosine A2A receptor, 5- hydroxytryptamine (5-HT)1A and 5-HT7 receptor densities in the front-parietal cortex in juvenile and adult rats. In receptor binding assay using [3H]CGS21680 and [3H]8-OH-DPAT, it was shown that neonatal pregnenolone-treatment induced a significant decrease in the adenosine A2A receptor density with no significant effects on the 5-HT1A and 5-HT7 receptor densities.
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PMID:Adenosine A2A, 5-HT1A and 5-HT7 receptor in neonatally pregnenolone-treated rats. 1172 92

In the CA3 region of rat hippocampal slices gamma-amino-butyric acid (GABA)(A/B) receptor antagonists induce low frequency bursting activity that was either inhibited (in 21% of slices) or increased by the selective 5-HT receptor agonists 5-carboxy-tryptamine (0.1-1 microM) and 8-hydroxydipropylaminotetralin (8-OH-DPAT). The selective 5-HT1A receptor antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexane carboxamide (WAY 100635) reversed the depression of bursting activity whereas the 5-HT7 receptor antagonist, (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970; 1-10 microM), but not the 5-HT1A, 4 or 6 receptor antagonists WAY100635 (10 microM), SB-204070 (10 microM) and SB-271046 (10 microM), reversed the increase in bursting activity. The apparent -log10 K(D) value (8.4) for the effect of SB-269970 was consistent with a selective action at 5-HT7 receptors. Accompanying the 5-CT-induced increase in bursting frequency there was a shortening of the burst event waveform and a reduction in the after-hyperpolarization following each bursting event both of which were inhibited by SB-269970. These effects appeared to result predominantly from a direct 5-HT(7) receptor-mediated inhibition of a Ca2+ activated K+ channel.
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PMID:5-HT7 receptors modulate synchronized network activity in rat hippocampus. 1175 Sep 18


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