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)

In rats allowed access to a 35% sucrose solution, following a 4-h period of food and water deprivation, an initial period of sucrose consumption was followed by a short period of grooming and exploratory behaviour, later superseded by resting. This "behavioural satiety sequence" was advanced in time by the 5-HT uptake inhibitors femoxetine and paroxetine and by the 5-HT1A/B agonist eltoprazine at anorectic and subanorectic doses. These effects, which are similar to those previously observed with another 5-HT uptake inhibitor, fluoxetine, are compatible with an increase in postprandial satiety.
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PMID:Effects of the 5-HT uptake inhibitors, femoxetine and paroxetine, and a 5-HT1A/B agonist, eltoprazine, on the behavioural satiety sequence. 153 13

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

Serotonergic drugs with 5-HT2 receptor agonist properties have been suggested to increase plasma vasopressin concentration, blood pressure (BP) and plasma renin activity (PRA). To study whether these actions are mediated by the same or different receptors, we used three potent 5-HT agonists with different structures and receptor binding profiles. All drugs were administered i.v. to conscious, unrestrained rats. The selective agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), which has high affinity for 5-HT2 receptors, caused marked increases in BP and PRA but no change in plasma vasopressin concentrations. The 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), which also binds to other 5-HT receptors, caused moderate increases in BP and PRA and significantly elevated plasma vasopressin concentrations. The 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), did not increase any of these parameters. BP and PRA elevations paralleled each other after all drugs, while vasopressin responses were clearly different. Vasopressin responses to m-CPP were entirely antagonised by the 5-HT1/5-HT2 antagonist metergoline, partially by the 5-HT2/5-HT1C antagonists ritanserin and LY 53857, but not by the 5-HT2 antagonist ketanserin. Ritanserin, LY53857 and ketanserin all very effectively blocked BP responses to m-CPP. These findings suggest that BP and PRA but not vasopressin responses are mediated by 5-HT2 receptors. Vasopressin secretion is mediated by 5-HT1 receptors, most likely by 5-HT1C receptors.
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PMID:Pharmacological characterization of serotonin receptor subtypes involved in vasopressin and plasma renin activity responses to serotonin agonists. 153 17

The hypothermia induced by the serotonin (5-HT)1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was attenuated in rats that had received a course of six electroconvulsive shocks (ECS) over a two-week period. The firing activity of dorsal raphe 5-HT neurons, as well as their responsiveness to microiontophoretic applications of 5-HT and 8-OH-DPAT, was unaltered in ECS-treated rats. The electrically evoked overflow of [3H]5-HT from preloaded slices of guinea pig hypothalamus was unchanged after the same ECS treatment. The concentration-effect curves of the 5-HT autoreceptor agonist 5-carboxyamidotryptamine (0.1-100 nM) were similar in slices prepared from control and ECS-treated guinea pigs. In addition, the reduction in the evoked [3H]5-HT overflow obtained by increasing the stimulation frequency from 1 to 5 Hz, which is due to a greater activation of terminal 5-HT autoreceptors at the higher frequency, was not altered by the ECS treatment. The enhancing effects of the 5-HT autoreceptor antagonist methiothepin (0.1-1 microM) and of the 5-HT3 agonist 2-methyl-5-HT (0.1-1 microM) on the evoked [3H]5-HT overflow were unaltered by the ECS treatment. These results thus indicate that repeated ECS attenuates the 8-OH-DPAT-induced hypothermia in rats, as previously reported, but does not affect the firing activity of 5-HT neurons and the sensitivity of their somatodendritic 5-HT1A autoreceptors in the dorsal raphe. The function of 5-HT terminals in the guinea pig hypothalamus was also unaffected by repeated ECS. In conclusion, repeated ECS does not affect the function of 5-HT neurons at the cell body and nerve terminal.
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PMID:Effect of repeated electroconvulsive shocks on serotonergic neurons. 153 97

The characteristics of 5-HT1A-recognition sites and receptor-mediated release of intracellular calcium were established in two transfected HeLa cell lines (HA 6 and HA 7) expressing different levels of human 5-HT1A receptors (about 3000 and 500 fmol/mg protein, Fargin et al. 1989; 1991; Raymond et al. 1989). The pharmacological profiles of the binding (determined with [3H]8-OH-DPAT) and the calcium response (measured using Fura-2) were clearly of the 5-HT1A type. Compounds such as 5-HT, 5-CT and 8-OH-DPAT acted as full agonists on the calcium response in both HeLa cell lines. In addition, methiothepin, pindolol, NAN 190 and SDZ 216-525 (Seiler et al. 1991) acted as silent and potent antagonists. Marked differences were observed in the responses mediated in the two cell lines. EC50 values of agonists (particularly 5-HT, 5-CT, flesinoxan and 8-OH-DPAT) were higher in HA 7 cells (up to 80-fold) than in other 5-HT1A receptor models (e.g. inhibition of adenylate cyclase in calf hippocampus). Further, a variety of compounds (ipsapirone, buspirone, spiroxatrine, MDL 73005) acted as agonists in HA 6 cells, whereas they behaved as silent antagonists in HA 7 cells (which express fewer receptors). By contrast, KB values for antagonists were comparable in HA 6 and HA 7 cells. The present data show that EC50 values and intrinsic activity for a given drug are subject to large variations depending on the number of receptors expressed in the target tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Agonist/antagonist interactions with cloned human 5-HT1A receptors: variations in intrinsic activity studied in transfected HeLa cells. 153 91

We used saturation radioligand binding to measure nine types of serotonin receptors in 13 neuroblastomas from children. 5-HT1E and 5-HT3 sites were found in neuroblastomas with receptor density and affinity similar to human or rat brain. No 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2, or 5-HT uptake sites were found in any of the tumors, although all were detected in human or rat brain. These data demonstrate that human neuroblastomas possess 5-HT receptors found in human brain and relevant to human myoclonus. We speculate that 5-HT receptors in human neural crest-derived tumors may have clinical and neurobiological significance.
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PMID:Serotonin receptors in human neuroblastoma: a possible biologic tumor marker. 153 97

Ten healthy subjects received buspirone (30 mg orally) with and without pre-treatment with the 5-HT1A receptor antagonist, pindolol (80 mg over 3 days). Following pindolol treatment the growth hormone and hypothermic responses to buspirone were significantly decreased. There was also a delay in the onset of the prolactin response to buspirone but the total amount of prolactin secretion, calculated as area under the curve, was not significantly reduced. The data suggest that the growth hormone and hypothermic responses to buspirone in humans are mediated by 5-HT1A receptors, but an explanation founded on pharmacokinetic factors cannot presently be excluded. Both this latter possibility and the lack of selectivity of pindolol for 5-HT receptors indicate the need for the further neuroendocrine studies of the mode of action of buspirone, preferably with more selective 5-HT1A receptor antagonists.
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PMID:Effect of pindolol on endocrine and temperature responses to buspirone in healthy volunteers. 157 Mar 92

Intracellular recordings were made from presumed dopamine-containing neurons in slices cut from the midbrain of the rat. Focal electrical stimulation produced a hyperpolarizing synaptic potential that was reduced by 75-95% by the GABAB-receptor antagonist 2-hydroxysaclofen (300 microM). 5-HT (3-100 microM) reduced the amplitude of the GABAB synaptic potential by 20-74%, with a 50% reduction at 10 microM, but did not reduce the amplitude of synaptic potentials mediated by GABAA receptors. 5-HT acted presynaptically because hyperpolarizations produced by exogenously administered GABA (1 mM) in picrotoxin (100 microM) were not affected by 5-HT (30 microM). (+/-)-Cyanopindolol (100 nM), a 5-HT1B antagonist, blocked the effect of 5-HT (10 microM); spiperone (1 microM), which is an antagonist at 5-HT1A and 5-HT2 receptors, had no effect. The amplitude of the GABAB synaptic potential was reduced by the 5-HT1B receptor agonists 1-[3-(trifluoromethyl)-phenyl]-piperazine (300 nM) and 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline (1 microM), but not by the 5-HT1A agonist N,N-dipropyl-5-carboxamidotryptamine (1 microM) or the 5-HT2 agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane (10 microM). We conclude that 5-HT activates presynaptic 5-HT1B receptors that inhibit the release of GABA onto GABAB but not GABAA receptors.
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PMID:5-hydroxytryptamine1B receptors block the GABAB synaptic potential in rat dopamine neurons. 157 82

In the presence of spiperone to block the 5-HT1A-mediated inhibition of pyramidal cell activity, 5-hydroxytryptamine (serotonin, 5-HT) produces a rapid transient increase in amplitude of the extracellularly recorded population spike from area CA1 of the hippocampus. Intracellular recording techniques in area CA1 of rat hippocampal slices were used to identify the ionic mechanism and to characterize the 5-HT receptor mediating this excitatory response to 5-HT. Most of the experiments were conducted in the presence of spiperone to block the 5HT1A hyperpolarization. Since spiperone also has high affinity for 5-HT2 receptors, any response mediated by 5-HT2 receptors would also be blocked. Bath perfusion of the slice with 5-HT increased the rectification of pyramidal cells in the subthreshold region, increased the resistance, and increased the amplitude of subthreshold excitatory postsynaptic potentials (EPSPs) to initiate spike firing. The 5-HT2,1C-selective agonist DOI mimicked this effect of 5-HT, and the 5-HT2,1C antagonist ketanserin (1 microM) blocked the effect of DOI. There was no change in the amplitude of the slow afterhyperpolarization (sAHP) or the amplitude of evoked inhibitory postsynaptic potentials (IPSPs). The increase in rectification and EPSP amplitude by 5-HT occurred even in the presence of the 5-HT4-selective antagonist BRL 24924 to prevent the decrease in amplitude of the sAHP by 5-HT. We conclude that 5-HT produces a fast excitatory response by increasing subthreshold conductance in CA1 hippocampal pyramidal cells. The identity of the receptor mediating this response was not conclusively identified, but resembled the 5-HT1C receptor.
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PMID:5-Hydroxytryptamine increases excitability of CA1 hippocampal pyramidal cells. 158 62

To study possible interactions between dopamine (DA) and serotonin (5-HT) neurochemical systems in the D-1 supersensitized induction of oral activity in neonatal 6-hydroxydopamine (6-OHDA) lesioned rats, the effects of a series of 5-HT agonists and antagonists were determined. At 3 days after birth rats were treated with desipramine HCl (20 mg/kg i.p., base form, 1 hr) and 6-OHDA HBr (100 micrograms, salt form, in each lateral ventricle). Rats were observed individually as adults, once a minute every 10 min over a 1-hr period after challenge with a DA or 5-HT receptor agonist. The respective 5-HT1A and 5-HT1B agonists, (+/-)-8-hydroxydipropylaminotetralin (0.50 mg/kg s.c.) and CGS 12066B maleate (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1, 2-alquinoxaline], 1:2 maleate salt; 3.0 mg/kg i.p.), did not increase oral activity. The mixed 5-HT1C and 5-HT2 receptor agonist, m-chlorophenylpiperazine (m-CPP), produced a slight increase in oral activity in control rats and a marked increase in oral activity in 6-OHDA-lesioned rats. In the 6-OHDA group the peak effect of 76.5 +/- 4.1 oral movements occurred with an m-CPP 2-HCl dose of 4.0 mg/kg. Pindolol (1.0 mg/kg i.p.), ketanserin tartrate (5 mg/kg i.p.) and MDL-72222 (3-tropanyl-3,5-dichlorobenzoate; 10 mg/kg s.c.), antagonists with high affinity for 5-HT1A,1B, 5-HT2 and 5-HT3 receptors, respectively, did not attenuate m-CPP actions. However, mianserin HCl (1.0 mg/kg s.c.), an antagonist with high affinity for 5-HT1C and 5-HT2 receptors, attenuated the oral response to m-CPP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Supersensitization of the oral response to SKF 38393 in neonatal 6-OHDA-lesioned rats is mediated through a serotonin system. 160 67


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