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)

High-affinity, specific [3H]5-hydroxytryptamine (5-HT) binding was analyzed in rat spinal cord homogenates. Drug competition studies were performed using 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) to compete selectively for 5-HT1A sites, RU 24969 to compete for 5-HT1B sites and mesulergine to compete for 5-HT1C sites. Competition data were analyzed by computer-assisted iterative curve-fitting analysis. The results demonstrate that 5-HT1A, 5-HT1B and 5-HT1C binding sites are present in rat spinal cord. In addition, approximately 33% of total 5-HT1 sites do not appear to represent either 5-HT1A, 5-HT1B or 5-HT1C binding sites. Therefore, 5-HT1D and/or some other 5-HT1 binding site subtype may also be present in rat spinal cord.
Brain Res 1987 Dec 08
PMID:Identification of 5-hydroxytryptamine binding site subtypes in rat spinal cord. 296 14

Extracellular electrophysiological recordings were obtained from rabbit retinal ganglion cells in either a superfused eyecup or an in vivo preparation. Selective antagonists or agonists of serotonin at the 5-HT2 or 5-HT1A receptors were applied, and the changes in light-evoked and spontaneous activity were studied. Both 5-HT1A agonists and 5-HT2 antagonists reduced the ON-components of the light-evoked responses of all classes of brisk ganglion cell; spontaneous activity was reduced in these cells as well. These results suggest that the indoleamine-accumulating amacrine cells of the rabbit retina serve to facilitate the output of the depolarizing rod bipolar cell and thereby increase the efficacy of transmission between this and other cells in the rabbit retina, and that this process is mediated by 5-HT2 receptors. On the basis of the similarity of the actions of the 2 classes of drug studied, we hypothesize further that 5-HT1A receptors mediate an inhibitory process that serves to terminate the indoleamine-induced facilitation. This process may be located either in the bipolar terminal or presynaptic to it in the terminal of the putative indoleaminergic cells.
J Neurosci 1987 Dec
PMID:The actions of serotonergic agonists and antagonists on the activity of brisk ganglion cells in the rabbit retina. 296 53

5-HT induced a hyperpolarization of the rat superior cervical ganglion in vitro which was resistant to both MDL 72222 (10 microM), a 5-HT3 antagonist, and ketanserin (1 microM), a 5-HT2 antagonist. The 5-HT1-selective ligands 5-carboxamidotryptamine and 8-OH-DPAT also hyperpolarized the ganglion. The 5-HT-induced hyperpolarization was potently antagonised by spiperone. These results suggest that 5-HT hyperpolarizes the rat superior cervical ganglion via a 5-HT1-like receptor which resembles the central 5-HT1A binding site.
Eur J Pharmacol 1987 Dec 15
PMID:A 5-HT1-like receptor mediates a sympathetic ganglionic hyperpolarization. 296 75

Separate groups of rats were trained to discriminate the stimulus properties of selective agonists at 5-HT receptors using a conditioned taste aversion procedure. Fluid-restricted rats were injected with drug or saline and then given access to a 0.25% saccharin solution for 30 min. When rats received a drug trial, saccharin consumption was followed by an injection of LiCl (1.8 mEq/kg i.p.), whereas on saline trials saccharin consumption was followed by a second injection of saline instead of LiCl. Rats were trained using injections of either 8-hydroxy-2-(di-n-propylamino)tetralin (0.4 mg/kg i.p.), an agonist selective for the 5-HT1A receptor, or 1-(m-trifluoromethylphenyl)piperazine (0.8 mg/kg i.p.), an agonist selective for 5-HT1B and 5-HT1C receptors, as the drug stimuli. Acquisition of the discriminated taste aversion, as measured by the differential effects on saccharin drinking between drug and saline trials, required only two to three pairings of either drug stimulus with LiCl injections. The 8-hydroxy-2-(di-n-propylamino)tetralin discriminative stimulus cue generalized to other drugs that are selective for the 5-HT1A receptor, such as ipsapirone (8-16 mg/kg i.p.) or buspirone (4 mg/kg i.p.), but not to agonists that are selective for the 5-HT1B/1C receptor, such as 1-(m-trifluoromethylphenyl)piperazine or 1-(m-chlorophenyl)piperazine. The discriminative stimulus properties of 1-(m-trifluoromethylphenyl)piperazine generalized to 1-(m-chlorophenyl)piperazine (0.2-0.8 mg/kg i.p.) but not to the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (0.4 mg/kg i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)
J Pharmacol Exp Ther 1988 Dec
PMID:Rapid discrimination of the stimulus properties of 5-hydroxytryptamine agonists using conditioned taste aversion. 297 86

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective serotonin1A (5-HT1A) receptor agonist, was studied for its anti-immobility activity in the forced swimming test when administered into the raphe nuclei medianus and dorsalis of rats. At concentrations ranging from 0.5 to 5 micrograms, 8-OH-DPAT significantly reduced the immobility of rats when administered into the nucleus raphe dorsalis, but only 5 micrograms was effective when administered into the nucleus medianus. The activity of rats in an open-field under conditions identical to those used in the forced swimming test was not significantly changed by various concentrations of 8-OH-DPAT administered into the nucleus raphe dorsalis, but was significantly increased by an infusion of 5 micrograms 8-OH-DPAT into the nucleus raphe medianus. The effect of an infusion of 1 micrograms 8-OH-DPAT into the nucleus dorsalis was prevented by infusing 2.5 micrograms (-)-propranolol or 2.5 micrograms (-)-pindolol into the same area 5 min before 8-OH-DPAT or by treating the animals with sulpiride systemically (100 mg/kg i.p.) or centrally (in the nucleus accumbens; 1 microgram/0.5 microliter). The results suggest that 8-OH-DPAT reduces the immobility of rats by activating dopamine transmission, probably in the nucleus accumbens, as a consequence of its ability to reduce the activity of 5-HT neurons that originate in the nucleus raphe dorsalis. In view of the similarities between the effects of well-established antidepressants and 8-OH-DPAT in the forced swimming test, it is suggested that 5-HT1A receptor agonists may constitute a novel class of antidepressant agents.
Eur J Pharmacol 1988 Dec 06
PMID:8-Hydroxy-2-(di-n-propylamino)tetralin, a selective serotonin1A receptor agonist, reduces the immobility of rats in the forced swimming test by acting on the nucleus raphe dorsalis. 297 8

The prejunctional and postjunctional 5-HT receptors of the canine saphenous vein were studied. The release of 3H-noradrenaline (3H-NA) from incubated saphenous vein strips was inhibited by 5-hydroxytryptamine (5-HT) in a concentration-dependent way (5-HT concentrations: 0.01, 0.1 and 1.0 mumol.l-1), but not by the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT; 1 and 10 mumol.l-1). The inhibitory effect of 5-HT was antagonized by metitepine and methysergide, but not by yohimbine, (-)-pindolol or ketanserin. In strips preincubated with 5-HT (1.2 mumol.l-1), the fractional release of 3H-NA was slightly reduced (paired experiments). 5-HT and 8-OH-DPAT caused concentration-dependent contractions of the saphenous smooth muscle. A parallel shift of the concentration-response curve for 8-OH-DPAT to the right was caused by metitepine and yohimbine, but not by ketanserin. The contractions caused by 5-HT were antagonized by metitepine and yohimbine (parallel displacement of the curves to the right), as well as by ketanserin and methysergide (with a depression of the upper part of the curve). Blockade of alpha-adrenoceptors (due to prazosin plus a low concentration of yohimbine) also resulted in a weak antagonistic effect. Ketanserin and metitepine displaced the noradrenaline concentration-response curve to the right. We conclude that the saphenous vein of the dog is endowed with prejunctional receptors of the 5-HT1 type which can not be classified as belonging either to the 1A or 1B subtype; and that at the postjunctional level 5-HT1 (possibly of the 1D subtype) and 5-HT2 receptors are present.(ABSTRACT TRUNCATED AT 250 WORDS)
Naunyn Schmiedebergs Arch Pharmacol 1988 Dec
PMID:The actions of 5-hydroxytryptamine receptor agonists and antagonists at pre- and postjunctional level on the canine saphenous vein. 297 24

This study examined whether pharmacological manipulation of serotonergic (5-HT) systems would affect the hypnotic action of flunitrazepam in rats. Flunitrazepam, a potent hypnotic, was used alone or combined with parachlorophenylalanine (pCPA), an inhibitor of the synthesis of 5-HT, 8-OH-DPAT, a 5-HT1A receptor agonist and fluvoxamine, an inhibitor of the reuptake of 5-HT. Flunitrazepam increased the amount of orthodox sleep, the latency of rapid eye movement (REM) sleep and decreased the amount of REM sleep. The drug pCPA decreased the total sleep time and the amount of orthodox and REM sleep. Administration of flunitrazepam to pCPA-pretreated rats induced orthodox sleep in an identical way to that found in the controls. The drug 8-OH-DPAT increased wakefulness and the latency of REM sleep. The association of flunitrazepam with 8-OH-DPAT abolished the increase in waking seen after 8-OH-DPAT alone. In contrast, the combined treatment with flunitrazepam and 8-OH-DPAT resulted in a lengthening of the latency of REM sleep significantly greater than that observed with the same dose of each drug alone. Fluvoxamine increased the latency a decrease the amount of REM sleep. The association of fluvoxamine with flunitrazepam induced a decrease in REM sleep, equal to the sum of the effects of the two drugs alone. Fluvoxamine did not modify the other effects of flunitrazepam. The present experiments demonstrate that the association of pCPA, 8-OH-DPAT and fluvoxamine, did not alter the hypnogenic effect of flunitrazepam. The possibility of an involvement of 5-HT mechanisms in the effect of flunitrazepam on the phasic events in sleep is questionable.
Neuropharmacology 1988 Dec
PMID:Hypnotic action of flunitrazepam in the rat: does 5-HT mechanism play a role? 297 26

The effects of the administration of L-triiodothyronine (T3) On the function of 5-HT in the CNS and its influence on the actions of electroconvulsive shock have been examined in mice. A single injection of T3 (100 micrograms/kg) had no effect 24 hr later on either 5-HT1A-mediated hypothermia, induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.5 mg/kg) or the 5-HT1B-mediated locomotor response to 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl) 1-H-indole (RU 24969; 50 ng i.c.v.). This treatment increased 5-HT2-induced head-twitches, produced by 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT; 2 mg/kg), but did not alter 5-HT2 receptors in the frontal cortex, suggesting that this potentiation was mediated indirectly through a modulatory neurotransmitter. One injection of T3 had no effect on the concentration of 5-HT in the forebrain or mid/hindbrain, but increased 5-HIAA in the latter region. Daily injections of T3 for 10 days attenuated the responses to both 8-OH-DPAT and RU 24969. Furthermore, 5-MeODMT-induced head-twitches returned to control values and this was accompanied by a 10% decrease in 5-HT2 receptors in the cortex. Repeated administration of T3 increased levels of 5-HT in mid/hindbrain and concentrations of 5-HIAA both here and in forebrain. Hence, treatment with T3 attenuated the function of 5-HT1A and 5-HT1B receptors, but increased 5-HT2-mediated responses, although the time-courses for these effects were different. Triiodothyronine also enhanced the synthesis and turnover of 5-HT in the brain of the mouse. Repeated electroconvulsive shock (90 V, 1 sec) decreased the hypothermia induced by 8-OH-DPAT. However, 5-MeODMT-induced head-twitches were enhanced by acute and repeated electroconvulsive shock. Administration of T3 together with electroconvulsive shock did not alter the effects of electroconvulsive shock on 5-HT1A-mediated hypothermia, but markedly potentiated its actions on 5-HT2-mediated responses. These findings provide possible pharmacological evidence for the suggested antidepressant effects of T3 and the potentiation of antidepressant therapy by this thyroid hormone.
Neuropharmacology 1988 Dec
PMID:The effects of acute and repeated administration of T3 to mice on 5-HT1 and 5-HT2 function in the brain and its influence on the actions of repeated electroconvulsive shock. 297 27

Radioligand binding studies were performed to characterize serotonin 5-HT1D receptors in postmortem human prefrontal cortex and caudate homogenates. [3H]5-HT binding, in the presence of pindolol (to block 5-HT1A and 5-HT1B receptors) and mesulergine (to block 5-HT1C receptors), was specific, saturable, reversible, and of high affinity. Scatchard analyses of [3H]5-HT-labeled 5-HT1D sites in human prefrontal cortex produced a KD value of 4.2 nM and Bmax of 126 fmol/mg protein. In competition experiments, 8-hydroxydipropylaminotetralin, trifluoromethylphenylpiperazine, mesulergine, 4-bromo-2,5-dimethoxyphenylisopropylamine, and ICS 205-930 had low affinity for [3H]5-HT-labeled 5-HT1D sites, indicating that the pharmacology of the 5-HT1D site is distinct from that of previously identified 5-HT1A, 5-HT1B, 5-HT1C, 5-HT2, and 5-HT3 sites. 5-HT1D sites in human brain have a similar pharmacology to the 5-HT1D sites previously identified in rat, porcine and bovine brains. Guanyl nucleotides, guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) and guanosine 5'-(beta, gamma-imido)-triphosphate (Gpp(NH)p), modulated the binding of [3H]5-HT to 5-HT1D sites, whereas adenyl nucleotides had no effect. These findings are supportive of the presence of serotonin 5-HT1D receptors in human prefrontal cortex and caudate which appear to be coupled to a GTP binding protein.
J Neurochem 1988 Dec
PMID:Serotonin 5-HT1D receptors in human prefrontal cortex and caudate: interaction with a GTP binding protein. 314 89

This investigation evaluated the effects of the 1-arylpiperazines (1-(1-naphthyl)piperazine (1-NP), 1-(2-[4-aminophenylethyl]-4-[3-trifluoromethylphenyl]piperazine (PAPP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP) and 1-(3-chlorophenyl)piperazine (mCPP) on head-twitching elicited by central 5-hydroxytryptamine2, (5-HT2) agonists and on the 5-HT motor syndrome associated with stimulating 5-HT1A receptors in rodents. 1-NP (0.25-16.0 mumol/kg i.p.) dose-dependently inhibited head twitching produced by carbidopa (100 mumol/kg i.p.) plus 5-hydroxy-L-tryptophan (1000 mumol/kg i.p.) in mice. Pretreatment with 4 mumol/kg of 1-NP shifted the entire dose-response curve for head-twitching induced by quipazine (0.33-46.7 mumol/kg i.p.) to the right without reducing locomotor stimulation produced by quipazine (8 mumol/kg) in mice placed in novel photocell cages. 1-NP, PAPP, TFMPP and mCPP (8 mumol/kg) antagonized twitching after 5-methoxy-N,N-dimethyltryptamine (100 mumol/kg i.p.) or 5-hydroxy-L-tryptophan. In rats, these arylpiperazines (1-32 mumol/kg) dose-dependently antagonized twitching elicited by quipazine (10 mumol/kg) without producing correlated alterations in locomotion. 1-NP, PAPP, and mCPP were equipotent and 6-fold more potent than TFMPP against twitching. None of these arylpiperazines caused twitching. 1-NP (4 mumol/kg) also antagonized twitching following the direct 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (6 mumol/kg i.p.) but not after the thyrotropin releasing hormone analog MK-771 (20 mumol/kg i.p.) in rats. Larger doses of 1-NP (4-32 mumol/kg) and PAPP (64 mumol/kg) but not TFMPP or mCPP (16-128 mumol/kg), also reduced the incidence of the 5-HT syndrome produced by 5-methoxy-N,N-dimethyltryptamine (30 mumol/kg) in rats.(ABSTRACT TRUNCATED AT 250 WORDS)
J Pharmacol Exp Ther 1988 Dec
PMID:Properties of some 1-arylpiperazines as antagonists of stereotyped behaviors mediated by central serotonergic receptors in rodents. 314 95


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