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)

The anti-immobility effect of imipramine (15 mg/kg) in the forced swimming test in mice was antagonized by the non-selective 5-hydroxytryptamine (5-HT) antagonist, metitepine (0.5 mg/kg), by the 5-HT1C/5-HT2 antagonist, mesulergine (15 mg/kg), and by the dopamine D2 antagonist, d,l-sulpiride (50 mg/kg). These three antagonists did not alter the behaviour of imipramine-treated mice in an open-field and did not reduce imipramine brain levels. The 5-HT2 antagonist, ritanserin (0.06 mg/kg), the 5-HT1A/5-HTB antagonist, l-propranolol (20 mg/kg), and the 5-HT3 antagonists, endo-2,3-dihydro-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2-oxo-1H- benzimidazole-1-carboxamide hydrochloride (DAU 6215; 0.1 mg/kg) and 1,2,3,9-tetrahydro-9-methyl-3[(2-methyl-1H-imidazol-1-yl)methyl]-4H- carbazol-4-one, HCl.2H2O) (GR 38032F; 0.1 mg/kg), failed to reduce imipramine-induced anti-immobility. Subthreshold doses of 8-hydroxy-2-(di-n-propylamino)tetralin hydrochloride (8-OH-DPAT; 0.5 mg/kg) and imipramine (7.5 mg/kg) did not synergize in reducing immobility. d,l-Sulpiride, but not mesulergine, antagonized the effect of desipramine (15 mg/kg) in the forced swimming test. All compounds were administered i.p. 6 min before imipramine or desipramine, given i.p. 30 min before the testing. Imipramine produced 50% inhibition of [3H]mesulergine binding to 5-HT1C receptors at 10 microM, a concentration below that obtained following i.p. imipramine administration. The results suggest a contribution of 5-HT1C receptors in the mechanism of the imipramine effect in the forced swimming test.
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PMID:Evidence that imipramine activates 5-HT1C receptor function. 177 22

1. 5-Hydroxytryptamine (5-HT) is able to potentiate the contractions induced by electrical field stimulation of pieces of human isolated urinary bladder. On the basis of available selective 5-HT agonists and antagonists, we have further investigated the receptors involved and their site of action. 2. 5-HT produced a concentration-dependent increase of the contractile response to electrical field stimulation from 0.1 nM to 1 microM. At higher concentrations (up to 100 microM) the effect decreased. These activities were mimicked by a variety of 5-HT agonists, for which the following rank order of potency was found: 5-HT greater than alpha-methyl 5-HT greater than 5-methoxytryptamine greater than 5-carboxamidotryptamine greater than 2-methyl 5-HT much greater than GR 43175. In addition the gastro-prokinetics agents metoclopramide, cisapride and the 5-HT3 antagonist ICS 205-930 behaved as 5-HT agonists, their EC50 values being 2.3, 0.3, and 0.5 (microM) respectively. 3. The 5-HT potentiating effect was resistant to antagonism by ondansetron (1 microM) and cyanopindolol (1 microM), selective 5-HT3 and 5-HT1A/1B antagonists respectively. The 5-HT2 antagonists ketanserin (1 microM), spiperone (1 microM) and methysergide (1 microM) also showed a weak inhibitory activity. Methiothepin (0.1-1 microM) antagonized only the inhibitory effect of 5-HT. Metoclopramide (0.1-1 microM), cisapride (0.01-0.1 microM) and ICS 205-930 (0.3-3 microM) all produced a rightward displacement of the 5-HT response curve with concomitant reduction of the maximum response. The pA2 values calculated were 7.4, 8.5 and 7.0 respectively. The antagonism of metoclopramide was receptor specific and was not apparently related to interactions with dopaminergic activity since domperidone showed no antagonism of 5-HT, and metoclopramide, itself, did not antagonize the potentiating effect of prostaglandin F2a.4. The receptor involved in the potentiating effect of 5-HT may be located prejunctionally because 5-HT did not potentiate responses to acetylcholine (ACh) or electrical field stimulation with the parameters of direct muscle excitation. Also, since the 5-HT potentiating effect was blocked by atropine, it may be attributed to a release of ACh.5. This study suggests that in the human urinary bladder 5-HT causes two opposite effects on the contractile response to electrical field stimulation. A potentiating effect at low concentrations due to an interaction with an atypical receptor, different from the classical 5-HT1, 5-HT2 or 5-HT3 subtypes and an inhibitory effect at greater concentrations probably due to an interaction with 5-HT1-like receptors. The possibility that this atypical receptor possesses some characteristics of those found in other isolated preparations like guinea-pig ileum, rat oesophagus and mouse embryo colliculi neurones is discussed.
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PMID:Pharmacological analysis of 5-hydroxytryptamine effects on electrically stimulated human isolated urinary bladder. 179 31

While it had no effect on the resting tension of mouse tracheal segments, 5-HT (10(-8)-10(-4) M) potentiated concentration dependently the contractions induced by electrical field stimulation (EFS). The maximal potentiation was 105 +/- 38% and the EC50 value was 1.4 +/- 0.6 x 10(-6) M (n = 6). The responsiveness of mouse trachea to acetylcholine was not altered by 5-HT (10(-5) M). The 5-HT1A,B antagonist pindolol (10(-6) M), the combined 5-HT2 and 5-HT1C receptor antagonist, ketanserin (10(-6) M), or the combined 5-HT1 and 5-HT2 receptor antagonist, methysergide (10(-6) M), all partially inhibited the effect of 5-HT on the twitch responses. Blockade of 5-HT3 receptors by GR 38032F (10(-6) M) did not affect the potentiation by 5-HT. Antagonism of 5-HT3 and 5-HT4 receptors by ICS 205,930 (3 x 10(-6) M) increased the potentiation of the twitch responses by 5-HT, this was probably due to a decrease of the baseline EFS-induced twitch response by ICS 205,930. Alkylation of the 5-HT2 receptor by phenoxybenzamine (3 x 10(-7) M) treatment did not significantly affect the potentiation of the twitch responses by 5-HT. The beta-adrenoceptor antagonist, timolol (10(-6) M), and the alpha-adrenoceptor antagonist, phentolamine (10(-6) M), did not influence the potentiation of the twitch responses by 5-HT, excluding the involvement of the adrenergic system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5-HT1-like receptors mediate potentiation of cholinergic nerve-mediated contraction of isolated mouse trachea. 179 65

Four major families of serotonin (5-hydroxytryptamine; 5-HT) receptors have been identified: 5-HT1, 5-HT2, 5-HT3 and 5-HT4. At this time, there is a general consensus that the 5-HT1 family can be further subdivided into 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, and 5-HT1P subpopulations. In addition, there are several other populations of less well-defined 5-HT receptors. The purpose of this presentation is to discuss 5-HT receptor nomenclature and the agents that are commonly used to investigate each receptor population in as much as it will serve to provide background for the remainder of the symposium. There is presently available an abundance of serotonergic agents; however, these agents are only semiselective, and none can be considered truly selective for a particular population of 5-HT receptors. As useful as these agents have been for the identification and characterization of 5-HT receptors, there remains a need for the development of new, more selective ligands.
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PMID:Serotonin receptors and their ligands: a lack of selective agents. 181 55

Binding studies with [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT), a specific serotonin1A (5-HT1A) receptor agonist, were done on the autopsied brains from control subjects and from patients with chronic schizophrenia. All the patients and controls were of the Japanese race. In the controls, representative Scatchard plots for the specific [3H]8-OH-DPAT bindings in the prefrontal cortex and hippocampus revealed a single component of high affinity binding site (Kd value = 5.7 and 5.9 nM, Bmax value = 80.1 and 101.0 fmol/mg protein, respectively). The [3H]8-OH-DPAT bindings to the prefrontal cortex and hippocampus were potently inhibited by serotonin (IC50 = 6.3 x 10(-9) M) and 5-HT1A agonists (IC50 = 5.0 x 10(-9) - 2.3 x 10(-7) M), while other neurotransmitters, 5-HT2 and 5-HT3 related compounds did not inhibit the binding (IC50 greater than 10(-5) M). The bindings were decreased in the presence of 0.1mM GTP and 0.1mM GppNHp but not in the presence of 0.1mM GMP. In the prefrontal and temporal cortices of schizophrenics, there was a significant increase in the specific [3H]8-OH-DPAT binding, by 40% and 60%, respectively, with no change in the hippocampus, amygdala, cingulum, motor cortex, parietal or occipital cortex, as compared to findings in the controls. Scatchard analysis showed that this increased binding reflects changes in the number of sites but not in the affinity. The effect of 0.1mM GppNHp on the binding to prefrontal cortex was observed in both controls and schizophrenic patients. The bindings were significantly greater in the schizophrenic patients than in controls, in the presence of 0.1mM GppNHp. Our findings suggest that there are GTP-sensitive 5-HT1A sites in the human brain and that selective increases in GTP-sensitive 5-HT1A sites in the prefrontal and temporal cortices of schizophrenics relate to the pathophysiology of schizophrenia.
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PMID:Increase in serotonin 5-HT1A receptors in prefrontal and temporal cortices of brains from patients with chronic schizophrenia. 182 56

This study pharmacologically characterizes a novel behavioral response as a potential in vivo model of serotonin (5-HT)1A receptor-mediated activity. In rats restrained in horizontal cylinders, the selective 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin HBr (8-OH-DPAT), dose-dependently (0.04-10.0 mg/kg s.c.) elicited spontaneous tail-flicks (STFs). This action was mimicked by other ligands possessing high affinity and high efficacy at 5-HT1A sites: RU 24969 [(5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole], lisuride, (+)-lysergic acid diethylamide and 5-methoxy-N,N-dimethyltryptamine hydrogen oxalate. The response could not be elicited by CGS 12066B [7-trifluormethyl-4-(4-methyl-l-piperazonyl)-pyrrolol- [1-2-a] quinoxaline dimaleate], mCPP 1-(3-chlorophenyl)-piperazine-2-HCl, TFMPPm-trifluromethylphenylpiperazine HCl, MK 212 [6-chloro-2-(l-piperzinyl)pyrazine], quipazine and DOI (+-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane HCl, which act in vivo as agonists at 5-HT1B, 5-HT1C and/or 5-HT2 receptors, or by the 5-HT3 agonist, 2-methyl-5-HT. p-chloroamphetamine, which releases endogenous 5-HT, also evoked STFs; in contrast, d-amphetamine, a preferential releaser of catecholamines, was inactive, as were agonists and antagonists at alpha-1, alpha-2, beta-1, beta-2, dopamine D1 and D2 sites. 8-OH-DPAT-elicited STFs were blocked by the 5-HT1/2 antagonist, methiothepin, but not by the 5-HT1C/5-HT2 antagonists, mianserin, ritanserin and ICI 169,369 [2-(2-dimethylaminoetheylthio)-3-phenylquinoline] nor by the 5-HT3 antagonists, GR 38032F [(1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-l-yl)methyl]-4H- carbazol-4-one HCl], ICS 205,930 [(3 alpha-tropanyl)-1H-indol-3-carboxylic acid ester] and MDL 72222 [(1 alpha H, 3 alpha, 5 alpha H)-tripan-3-yl-3,5- dichlorobenzoate]. beta-Blockers with 5-HT1A affinity i.e., (-)-alprenolol, (+/-)-isamoltane and, stereoselectivity, (-)-but not (+)-pindolol, blocked the action of 8-OH-DPAT. Spiperone and spiroxatrine, D2 antagonists with high 5-HT1A affinity, also inhibited 8-OH-DPAT-induced STFs. Selective beta-blockers and D2 antagonists with low 5-HT1A affinity were inactive. 5-HT1A partial agonists, the pyrimidinylpiperazines, buspirone, gepirone and ipsapirone, the halogenated phenylpiperazine, LY 165,163 [1-(2-(4-aminophenyl) ethyl-4-(3-trifluoromethylphenyl)-piperazine], and the benzodioxane, MDL 72832 [8-(4-(1,4-benzodioxan-2-yl-methylamino)-butyl-8-azaspiro-(4 ,5)-decane- 7,9-dione] did not elicit STFs and antagonized the effect of 8-OH-DPAT.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:5-hydroxytryptamine (5-HT)1A receptors and the tail-flick response. I. 8-hydroxy-2-(di-n-propylamino) tetralin HBr-induced spontaneous tail-flicks in the rat as an in vivo model of 5-HT1A receptor-mediated activity. 182 33

1. Serotonin (5-HT) and selective 5-HT receptor agonists were administered intrathecally (i.t.) in rats, and the antinociceptive efficacy of these agents was assessed on the tail-flick and hot plate tests. 2. The 5-HT receptor agonists examined in this study included the 5-HT1A agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT), the 5-HT1B agonist m-trifluoromethylphenylpiperazine (TFMPP), the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and the 5-HT3 agonist phenylbiguanide (PBG). 3. None of these agents produced significant elevations in tail-flick latency (TFL) at doses which produced elevations in hot plate latency (HPL). 4. In contrast, the i.t. dose of 5-HT which elevated TFL also produced analgesia on the hot plate test. 5. Serotonin-induced elevations in TFL were reversed by pindolol, ritanserin and ICS 205-930, suggesting that 5-HT interacts with more than one 5-HT site in the spinal cord to produce analgesia on the tail-flick test. 6. The finding that ritanserin reversed 5-HT-induced elevations in HPL suggests that the 5-HT2 site is primarily responsible for mediating the spinal antinociceptive effects of 5-HT on the hot plate test.
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PMID:Analgesic effects of serotonin and receptor-selective serotonin agonists in the rat spinal cord. 182 46

Subcutaneous administration of the prototypical 5-HT1-like agonist, 5-carboxamidotryptamine (5-CT), increased 2-h water intake by nondeprived rats (ED50 = 0.04 mumol/kg). The 5-HT1 agonists 8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT, 0.04-0.32 mumol/kg) and RU 24969 (0.16 mumol/kg) did not produce drinking. The dipsogenic effect of 5-CT (0.08 mumol/kg) was prevented by the 5-HT1/2 antagonist, methysergide (ID50 = 4 mumol/kg), but not by 16 mumol/kg of the 5-HT2 antagonist, ketanserin; the 5-HT21C antagonist, mianserin; or the 5-HT3 antagonist, MDL 72222, 5-CT also increased drinking and reduced food intake when food-deprived rats were given 2-h access to mash. Methysergide (16 mumol/kg) inhibited both actions of 5-CT but an equimolar dose of the 5-HT1/beta adrenergic antagonist, (-)-propranolol, blocked only the drinking. The 5-HT21C antagonist, ritanserin (16 mumol/kg), altered neither ingestive action of 5-CT although, by itself, ritanserin increased mash intake. The results suggest that activating a subtype of peripheral 5-HT1-like receptor stimulates drinking in rats. This receptor is unlike either the 5-HT1A or the 5-HT1C sites found in the brain. Furthermore, the dipsogenic and anorectic actions of 5-CT occur independently.
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PMID:Peripheral 5-carboxamidotryptamine (5-CT) elicits drinking by stimulating 5-HT1-like serotonergic receptors in rats. 182 33

1. Acetylcholine (ACh) release from the cerebral cortex of freely moving guinea-pigs, implanted with epidural cups, was studied. 2. A single dose of chlorimipramine (Cl-Imip, 10 mg kg-1, s.c.), reduced the cortical ACh release both in normal and in chronically (10 mg kg-1 daily, s.c., for 14 days) Cl-Imip-treated guinea-pigs; the 5-HT3 antagonist MDL 72222 (1 mg kg-1, s.c.) antagonized this effect. 3. A single dose of Cl-Imip significantly reduced the effect of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylaminotetralin) (8-OH-DPAT, 0.1 mg kg-1, s.c.), which nearly doubled the cortical ACh release in control animals. MDL 72222 restored to normal the response to 8-OH-DPAT reduced by the anti-depressant. 4. A single dose of Cl-Imip did not change the inhibitory, MDL 72222-sensitive, effect induced by the 5-HT3 agonist 2-methyl-5-hydroxytryptamine (2-methyl-5-HT, 500 micrograms, i.c.v.). 5. In chronically Cl-Imip-treated guinea-pigs, the facilitatory effect of 8-OH-DPAT was no longer present, while the inhibitory, MDL 72222-sensitive, effect of 2-methyl-5-HT was maintained. 6. These results indicate that the 5-HT1A receptor-mediated increase in ACh release is reduced by prolonged Cl-Imip treatment, while the 5-HT3 receptor-mediated inhibition of ACh release is unaffected. The relevance of these findings to the antidepressant mechanism of Cl-Imip is discussed.
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PMID:Influence of acute and chronic chlorimipramine treatment on the 5-HT receptor-mediated modulation of acetylcholine release from the cerebral cortex of freely moving guinea-pigs. 183 Feb 35

Three pharmacologically distinct high-affinity [3H]serotonin ([3H]5-HT) binding sites were identified in spinal cord synaptosomes. [3H]5-HT competition studies using selective 5-HT1A receptor ligands indicated that approximately 25% of high-affinity synaptosomal [3H]5-HT binding was inhibited by 5-HT1A-selective compounds, an estimate consistent with [3H](+-)-8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) saturation experiments in which 5-HT1A receptors were directly labeled. [3H]5-HT competition studies using high-affinity 5-HT1B compounds performed in the presence of 100 nM 8-OH-DPAT (to block 5-HT1A receptors) indicated that approximately 26% of all specific, high-affinity [3H]5-HT binding to spinal cord synaptosomes was to 5-HT1B receptors. [3H]5-HT competition studies performed in the presence of 100 nM 8-OH-DPAT and 10 nM RU 24969 (to block 5-HT1A and 5-HT1B receptors, respectively) indicated that the remaining 49% of [3H]5-HT binding did not possess the pharmacologic profile previous reported for 5-HT1C, 5-HT1D, 5-HT1E, 5-HT2, or 5-HT3 receptors. This residual 49% of [3H]5-HT binding to spinal cord synaptosomes observed in the presence of 100 nM 8-OH-DPAT and 10 nM RU 24969 (subsequently referred to as "5-HT1S") displayed high affinity and saturability (KD = 4.7 nM) in association/dissociation and saturation experiments. Addition of 300 microM GTP or the nonhydrolyzable form of GTP, 5'-guanylylimidodiphosphate, inhibited [3H]5-HT binding to 5-HT1S receptors in saturation experiments by 35 and 57%, respectively, whereas ATP was without effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of a novel serotonin receptor subtype (5-HT1S) in rat CNS: interaction with a GTP binding protein. 183 2


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