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)

Although numerous subtypes of serotonin [5-hydroxytryptamine (5-HT)] receptors have been identified in the newborn rat by radioligand binding studies, there have been few studies of the functional significance of these early receptors, most without the benefit of selective drugs. We performed acute dose-response and time course behavioral studies in 1-day-old rats with the putative selective agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (5-HT1A), 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H-indole (RU 24969) (5-HT1B), and (+-)1-(2,5-dimethoxy-4-iodo-phenyl aminopropane)-2 (DOI) (5-HT2/1C). The agonists induced distinctive behavioral syndromes. The DOI syndrome mainly included rudiments of forepaw myoclonus and dystonic limb postures, but no shaking behavior (head shakes or wet-dog shakes) or spinal myoclonus, two key reference behaviors for its effects in adult rats. The most distinctive feature of the 8-OH-DPAT-induced syndrome was flat body posture. RU 24969 most significantly increased locomotor activity, inducing propulsive movements with episodic rests and sudden hindlimb jerks. These studies suggest that functional and differential activity of 5-HT1A, 5-HT1B, and 5-HT2/1C receptors occurs much earlier in the rat than previously appreciated. The absence of DOI-induced shaking behavior and spinal myoclonus, however, suggests incomplete maturation at the level of the receptor or effector pathways for these behaviors.
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PMID:Serotonin receptor ontogeny: effects of agonists in 1-day-old rats. 147 12

Intracellular recording methods were used to study the actions of 5-hydroxytryptamine (5-HT) on 257 myenteric neurons in the guinea pig gastric antrum. Application of 5-HT caused three types of postsynaptic responses. A fast-activating depolarizing response was accompanied by a decreased input resistance and desensitized quickly to repeated applications. It was mediated by a 5-HT3 receptor. A slowly activating depolarization, accompanied by an increase in the input resistance and enhancement of the excitability, was mainly observed in after hyperpolarizing/type 2 neurons. It was suppressed by the prokinetic benzamide compound renzapride, while classical 5-HT1-4 receptor antagonists had no effect, suggesting the involvement of a 5-HT1p receptor as described in small intestinal neurons. A long-lasting hyperpolarizing response, accompanied by a decreased input resistance, was observed in a small subset of neurons. This response seemed to be mediated by a 5-HT1a receptor. Superfusion of 5-HT caused a dose-dependent inhibition of the stimulus-evoked nicotinic cholinergic fast excitatory postsynaptic potential (EPSP), which was mediated by a presynaptic 5-HT1a receptor. 5-HT also presynaptically inhibited the slow EPSP.
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PMID:Actions of 5-hydroxytryptamine on myenteric neurons in guinea pig gastric antrum. 147 91

A new potent, selective and p.o. active serotonergic [5-hydroxytryptamine (5-HT2)] receptor antagonist, SR 46349B [trans, 4-([3Z)3-(2-dimethylaminoethyl)oxyimino-3(2-flurophenyl++ +)propen-1-yl]phenol hemifumarate) has been characterized by a series of "in vitro" and "in vivo" methods. Based upon binding studies with 5-HT2 receptors in rat brain cortical membranes and blockade of 5-HT-induced contractions in isolated tissues (rabbit thoracic aorta, rat jugular vein, rat caudal artery, rat uterus and guinea pig trachea), SR 46349B showed high affinity for 5-HT2 receptors. Furthermore, SR 46349B displayed moderate affinity for the 5-HT1C receptor and had no affinity for the other 5-HT1 subclass (5-HT1A, 5-HT1B or 5-HT1D), dopamine (D1 or D2), "alpha" adrenergic (alpha-1 or alpha-2), sodium and calcium channel and histamine (H1) receptors. It did not interact with histamine (H1), alpha-1 adrenergic and 5-HT3 receptors in smooth muscle preparations. No inhibition of the uptake of norepinephrine, dopamine or 5-HT was seen. Based upon blockade of pressor responses to 5-HT in pithed rats and in vivo binding studies in mice, SR 46349B was found to be a potent and p.o. active 5-HT2 receptor antagonist with a relatively long duration of action. Behavioral experiments, including mescaline- and 5-hydroxytryptophan-induced head twitches and learned helplessness, as well as sleep-waking cycle and EEG spectral parameter studies, indicated that SR 46349B has a classical 5-HT2 psychopharmacological antagonist profile.
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PMID:Biochemical and pharmacological properties of SR 46349B, a new potent and selective 5-hydroxytryptamine2 receptor antagonist. 150 Nov 21

Auditory evoked middle latency responses recorded in the hippocampus (HAER), were monitored in alert, gently restrained rats with chronic indwelling electrodes and cannulae. Intrahippocampal (i.h.) injection of 5-hydroxytryptamine (5-HT, 10 micrograms) reduced the amplitude and increased the latency of the N28 and P55 peaks of the HAER. An early (P18) negative peak was unaffected. Buspirone (1 microgram, i.h. and 3 mg/kg, i.p.) had similar effects to those produced by i.h. 5-HT. RU 24969 (1 mg/kg, s.c.) also reduced the amplitude of the N28 peak of the HAER. Long-term treatment with buspirone for 14 days at a dose (0.5 mg/kg, i.p.) which when applied acutely did not produce any observable effect, caused an increase in the latency of both the N28 and P55 peaks. Direct i.h. injection of 5-HT into these chronically treated animals did not have any additional depressant effect on the HAER peaks. It is concluded that these serotoninergic agonists can modulate the later peaks of the HAER possibly via 5-HT1A receptors. In the case of buspirone there was evidence of an enhanced depressant effect following chronic treatment [corrected].
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PMID:Serotoninergic depression of auditory evoked responses recorded in the rat hippocampus: effect of repeated buspirone treatment. 150 59

The study concerned the effects of 5-hydroxytryptamine (5-HT) on intragastric pressure in bilaterally vagotomized spinal rats. Intravenous (i.v.) bolus injections of 5-HT (2.5, 5.0 and 10 micrograms/kg) produced dose-dependent increases in intragastric pressure; these effects were not modified by atropine (up to 0.2 mg/kg) or mepyramine (1 mg/kg), but were blocked by the mixed 5-HT1-like and 5-HT2 receptor antagonists, methiothepin (0.1, 0.3 and 0.5 mg/kg i.v.) and methysergide (0.5, 1 and 2.5 mg/kg i.v.). However, metergoline (0.5, 1 and 2 mg/kg i.v.) did not markedly modify this effect of 5-HT; only the response induced by 5 micrograms/kg 5-HT was significantly antagonized by the highest dose of metergoline. In contrast, neither the 5-HT2 receptor antagonist, ketanserin (0.5, 1 and 1.5 mg/kg i.v.), nor the 5-HT3 receptor antagonist, ICS 205-930 (0.5, 1 and 3 mg/kg i.v.), influenced the 5-HT-induced increase in intragastric pressure. In addition, 5-carboxamidotryptamine (25, 50 and 100 micrograms/kg i.v.) and RU 24969 (50, 100 and 200 micrograms/kg i.v.) mimicked the aforementioned effects of 5-HT but were weaker than 5-HT. These data suggest that the 5-HT-induced increase in intragastric pressure in the spinal and bilaterally vagotomized rat is mediated by an atypical 5-HT1-like receptor, which, based on the low agonist potency of 5-carboxamidotryptamine and RU 24969 and the resistance to blockade by metergoline, does not seem to correspond to either the 5-HT1A, 5-HT1B, 5-HT1C or the 5-HT1D receptor subtypes.
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PMID:Role of 5-HT1-like receptors in the increase in intragastric pressure induced by 5-hydroxytryptamine in the rat. 152 63

5-Hydroxytryptamine (5-HT) was injected into the rostral ventrolateral medulla (RVLM) in urethane-anaesthetized rats and its effect assessed on thermoregulatory and non-thermoregulatory cutaneous circulations by the measurement of skin surface temperatures. 5-Hydroxytryptamine (5-50 nmol) produced a dose-related fall in blood pressure (5-20 mmHg) and an increase in tail and plantar foot surface temperatures, indicative of dilatation in the underlying cutaneous circulations. If heat was not applied to the animal, the body temperature fell by 1-2 degrees C within 15-25 min. The decrease in tail and foot temperatures, produced by low frequency (25 Hz, 5 min) electrical stimulation, was antagonized by the injection of 5-HT at the site of stimulation. 5-Carboxyamidotryptamine (2.5-20 nmol) and flesinoxan (5-25 nmol) produced responses similar to 5-HT. The 5-HT2 receptor agonist, alpha-methyl 5-hydroxytryptamine (alpha-methyl 5-HT, 5.5-100 nmol) was only effective in increasing tail and plantar foot temperatures, at dose levels above 25 nmol. However, in a few sites restricted to the anterior region of the RVLM, alpha-methyl 5-HT (11 nmol) evoked a small decrease in tail and foot temperatures, indicative of a constrictor effect, without influencing resting cardiovascular parameters. The results are discussed in relation to the central mechanisms which underly the hypothermia and hyperthermia produced by 5-HT1A and 5-HT2 receptor agonists.
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PMID:Changes in the tail surface temperature of the rat following injection of 5-hydroxytryptamine into the ventrolateral medulla. 152 3

Single s.c. injections of the 5-hydroxytryptamine (5-HT)1A receptor agonists buspirone at 4 mg/kg, 8-hydroxy-2-(di-n-propylamino)tetralin at 1 or 4 mg/kg or ipsapirone at 10 mg/kg did not affect 5-HT inhibition of forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes. However, a single injection of buspirone at 8 mg/kg, and daily injections of each of the agonists for 8 days, resulted in a reduction in the degree of enzyme inhibition by 5-HT. Chronic administration of the antidepressants fluoxetine, zimelidine and maprotiline by i.p. injections at 15 mg/kg for 3 weeks also resulted in a decreased degree of enzyme inhibition. Chronic iprindole at the same dose had no effect. It is concluded that the antidepressant-like properties of 5-HT1A receptor agonists may be mediated partly by a postsynaptic action at the level of serotonergic second messenger transduction in the hippocampus.
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PMID:Regulation of 5-hydroxytryptamine1A receptor function in rat hippocampus by short- and long-term administration of 5-hydroxytryptamine1A agonist and antidepressants. 153 Sep 73

Synaptosomes prepared from freshly obtained human cerebral cortex and labeled with [3H]choline have been used to investigate the modulation of [3H]acetylcholine ([3H]ACh) release by 5-hydroxytryptamine (5-HT). The Ca(2+)-dependent release of [3H]-ACh occurring when synaptosomes were exposed in superfusion to 15 mM KCl was inhibited by 5-HT (0.01-1 microM) in a concentration-dependent manner. The effect of 5-HT was mimicked by 1-phenylbiguanide, a 5-HT3 receptor agonist, but not by 8-hydroxy-2-(di-n-propylamino)tetralin, a 5-HT1A receptor agonist. The 5-HT3 receptor antagonists tropisetron and ondansetron blocked the effect of 5-HT, whereas spiperone and ketanserin were ineffective. It is suggested that cholinergic axon terminals in the human cerebral cortex possess 5-HT receptors that mediate inhibition of ACh release and appear to belong to the 5-HT3 type.
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PMID:5-Hydroxytryptamine3 receptors sited on cholinergic axon terminals of human cerebral cortex mediate inhibition of acetylcholine release. 153 19

Earlier studies have indicated that the sympathoadrenal system and the corticotropic axis control brain levels of tryptophan (Trp), the precursor of 5-hydroxytryptamine (5-HT). We investigated the effects of 5-HT receptor agonists known to activate the sympathoadrenal system and/or the corticotropic axis on plasma and brain Trp levels. Neither the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.5 mg/kg s.c.), nor the 5-HT1C receptor agonist 1-(3-chlorophenyl)piperazine (mCPP, 2.5 mg/kg s.c.) affected plasma and brain Trp levels. The 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI, 0.5-2 mg/kg s.c.) increased brain Trp levels, an effect which was significant for the two highest doses used (1.5-2 mg/kg s.c.).
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PMID:The 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane increases brain tryptophan levels in the rat. 153 38

In this study, we have investigated serotonin hyperalgesia employing the mechanical paw withdrawal nociceptive threshold test in the rat. Intradermally injected serotonin was found to produce a dose-dependent hyperalgesia that was not attenuated by procedures which eliminate the known indirect mechanisms of hyperalgesia such as sympathectomy, polymorphonuclear leukocyte depletion or cyclooxygenase inhibition. In addition, the latency to onset of serotonin hyperalgesia is extremely short, with maximal hyperalgesia observed in less than 1 min, a similar temporal onset to direct-acting hyperalgesic agents such as prostaglandin E2. The results suggest, therefore, that the hyperalgesic effects of serotonin in our animal model are exerted by direct action on primary afferent neurons. Only the intradermal injection of selective serotonin (5-hydroxytryptamine; 5-HT) agonists for the 1A receptor subset (5-HT1A), (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthaline hydrobromide and N,N-dipropyl-5-carboxamido-tryptamine maleate, produced dose-dependent hyperalgesia. No hyperalgesia was seen after 5-HT1B, CGS-12066B maleate and m-trifluoromethylphenyl-piperazine hydrochloride; 5-HT2+IC, alpha methyl 5HT and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl; or 5-HT3, 2-methyl-5-hydroxytryptamine maleate and phenylbiguanide, agonists. Similarly, only the 5-HT1A antagonists, spiroxatrine and spiperone, attenuated the hyperalgesia induced by intradermally injected serotonin. 5-HT2+IC antagonists, mesulergine and ketanserin, and 5-HT3 antagonists, quipazine and 3-tropanyl-indole-3-carboxylate, did not significantly attenuate 5-HT hyperalgesia. We conclude that serotonin produces hyperalgesia by a direct action on the primary afferent neuron via the 5-HT1A subset of serotonin receptors.
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PMID:Serotonin is a directly-acting hyperalgesic agent in the rat. 153 74


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