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 actions of 5-hydroxytryptamine (5-HT) on the electrically induced twitch responses of mouse vas deferens were studied. 5-HT at the concentration range of 10(-8) to 10(-4) M produced a "bell-shaped" concentration-response curve on the field-stimulated twitch contractions; the enhancement of the contractions was maximum at 10(-5) M and progressively reduced at the concentrations of more than 10(-5) M. In the presence of ketanserin, whereas the stimulatory response to low concentrations of 5-HT (less than or equal to 10(-6) M) was not changed, that to high concentrations was reversed. The stimulation by 5-HT (less than or equal to 10(-5) M) was principally antagonized by MDL 72222. In the presence of both MDL 72222 and ketanserin, 5-HT inhibited the twitch contractions in a dose-dependent manner. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and BP-554 (1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine), selective 5-HT1A agonists, only inhibited the twitch contractions. Downward slope of the contraction-response curve of 5-HT (greater than or equal to 10(-5) 5 M) was shifted to right in the presence of 8-OH-DPAT. 5-HT and 8-OH-DPAT had no effect on the tension of unstimulated organs. Contractions elicited by ATP were potentiated by 5-HT, which was antagonized by ketanserin. 8-OH-DAPT did not affect ATP-elicited contractions. These results suggest the presence of presynaptic 5-HT1, maybe 5-HT1A and 5-HT3 receptors mediating inhibition and potentiation, respectively, of neurotransmitter release and of postsynaptic responsible for enhancing neurogenic contractions in mouse vas deferens.
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PMID:5-Hydroxytryptamine modulation of electrically induced twitch responses of mouse vas deferens: involvement of multiple 5-hydroxytryptamine receptors. 239 4

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) is a selective 5-HT1A serotonin agonist. Derivatives of 8-OH-DPAT with amine substituents larger or more bulky than n-propyl appear to be inactive in a presynaptic biochemical assay measuring agonist-induced feedback inhibition of 5-HT synthesis but have never been examined in brain binding assays. A series of N-phenylalkyl derivatives of 8-methoxy-2-aminotetralin was evaluated at [3H]-8-OH-DPAT-labeled 5-HT1A sites in rat brain hippocampal membranes. All of the phenylalkyl derivatives displayed significant affinity for these sites and, of the agents examined, the 3-phenylpropyl 8-hydroxy analogue appears to be optimal and had an affinity (Ki = 1.9 nM) comparable to that of 8-OH-DPAT (Ki = 1.2 nM). In addition, the presence of an oxygen-containing substituent at the 8-position of the tetralin ring is not necessary for good affinity, and secondary amines and tertiary amines displayed equal affinity at central 5-HT1A binding sites. 5-HT1A sites are found both pre- and postsynaptically; thus, differences observed in the biochemical assay as compared to the results of the present binding study could be due to different structural requirements of these two receptors. This seems unlikely, however, because there was little difference in the affinities of several selected analogues for striatal versus hippocampal binding sites. Because we have now demonstrated that amine substituents larger than propyl, and an unsubstituted 8-position, are well tolerated by central 5-HT1A sites, future studies aimed at the development of new serotonergic tetralin analogues need not be limited to N-propyl or 8-hydroxy derivatives of 2-aminotetralin.
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PMID:2-(Alkylamino)tetralin derivatives: interaction with 5-HT1A serotonin binding sites. 252 Dec 52

The modulatory role of serotonin (5-HT) on the acoustic startle reflex was studied using 5-HT receptor agonists and antagonists. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) (1,2 and 4 mg/kg, SC) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (1,2 and 4 mg/kg, IP), putative 5-HT1a receptor agonists, increased the magnitude of the startle reflex, while quipazine (5, 10 and 20 mg/kg, SC), an agonist with mixed 5-HT2 and 5-HT1b receptor activity, decreased startle responsiveness. Pretreatment of rats with ketanserin (1, 2 and 4 mg/kg, SC), a 5-HT2 receptor antagonist, had no significant effect on the activity of 8-OHDPAT, 5-MeODMT, or quipazine. Metergoline (0.25, 0.5, 1 and 2 mg/kg, SC), a mixed 5-HT1/5-HT2 receptor antagonist attenuated the augmentation of the reflex by 8-OHDPAT and 5-MeODMT and the suppression produced by quipazine. At the doses used, metergoline produced a non-dose-dependent increase in startle, while ketanserin had no effect. None of the agents specifically affected the ability of a prepulse stimulus to inhibit the acoustic startle response. These data suggest that 5-HT1a and 5-HT1b receptors play opposite roles in the modulation of the acoustic startle response and that 5-HT plays little, if any, role in the prepulse inhibition of the acoustic startle response.
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PMID:The role of 5HT1A receptors in the modulation of the acoustic startle reflex in rats. 252 58

Intracellular recordings were made from rat locus ceruleus neurons in the slice preparation in vitro. Depolarizing synaptic potentials (DSP)2 elicited by electrical stimulation were typically 10 to 15 mV in amplitude and 200 msec in duration. Superfusion with 5-hydroxytryptamine (5-HT, serotonin) or the 5-HT1 receptor agonist 5-carboxamidotryptamine (5-CT), produced an inhibition of the DSP. The maximal inhibition was 55 +/- 2% (mean +/- S.E.M.). The EC50 for 5-CT was 60 nM, whereas for 5-HT it was 12 microM. Cocaine (10 microM) shifted the 5-HT concentration-response curve to the left and the EC50 to 320 nM. 8-Hydroxy-2-(di-n-propylamino)tetralin, a selective 5-HT1A receptor ligand, also inhibited the DSP, but only produced about 65% of the maximal 5-CT or 5-HT response (EC50 = 50 nM). A relatively selective 5-HT1B ligand (65-fold 5-HT1B greater than 5-HT1A), 1-(m-trifluoromethyl-phenyl)-piperazine, acted as a full agonist (EC50 = 110 nM). None of these compounds had any effects on the membrane properties of the cell at the doses tested. The response to 8-hydroxy-2-(di-n-propylamino) tetralin was antagonized by pretreatment with the 5-HT1A antagonist spiperone (1 microM). The estimated KD for spiperone was 16 nM. At this same concentration, however, there was no effect on the 5-CT-induced inhibition. The antagonist 4-(3-ter-butyl-amino-2-hydroxy-propoxyl)-indol-2-carbonic acid isopropyl ester (LM 21-009, 100 nM) was found to be a partial agonist producing a 26 +/- 4% inhibition of the DSP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin agonists inhibit synaptic potentials in the rat locus ceruleus in vitro via 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptors. 252 17

The involvement of serotonin (5-HT) in modulating the acoustic startle response (ASR) is well established in adult rats, but 5-HT involvement during the preweaning period, when 5-HT neurons undergo extensive development, has not previously been described. Three 5-HT receptor subtypes are reported to modulate the ASR in adult rats: 5-HT1A and 5-HT2 receptor agonists facilitate the ASR, whereas 5-HT1B agonists decrease the response. In the present study, the effects of 5-HT agonists and generalized 5-HT depletion on the ASR were studied in preweanling animals, using independent groups of Long-Evans rats tested on postnatal day (PND) 13, 17 and 21. 8-Hydroxy-2-(di-n-propylamino) tetralin (8OHDPAT, 62-1000 micrograms/kg), a 5-HT1A receptor agonist, and 5-methoxy-N,N-dimethyl tryptamine (MeODMT, 2-4 mg/kg), a nonselective 5-HT agonist, had no effect on PND 13 and then increased the ASR on PND 17 and 21. The 5-HT2 receptor antagonists cyproheptadine (5 mg/kg) and ketanserin (5 mg/kg) blocked the effect of MeODMT at both ages, providing some evidence that MeODMT increased the ASR through 5-HT2 receptors. 1-(m-Chlorophenyl) piperazine (mCPP, 1-5 mg/kg), a 5-HT1B agonist, had no effect on ASR amplitude on PND 13 or 17 and then produced a dose-related decrease in the response on PND 21. Generalized depletion of 5-HT by 80-90% in whole-brain and spinal cord, using p-chlorophenylalanine (PCPA, 300 mg/kg 24 hr prior to testing), did not alter ASR amplitude at any age.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonergic modulation of the acoustic startle response in rats during preweaning development. 253 May 91

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and RU 24969 have been used to investigate whether 5-HT1A and 5-HT1B receptors are involved in the naloxone-induced jumping behaviour of the chronically morphine-dependent mouse. To control for possible interactions with catecholaminergic systems, the effects of alpha 1- and alpha 2-adrenoceptor antagonists were investigated. 8-OH-DPAT and RU 24969, as well as buspirone, ipsapirone and flesinoxan, were found to suppress jumping. The effects were mimicked by the alpha-adrenoceptor antagonists, idazoxan, WY 26392, yohimbine and rauwolscine. Inhibition of 5-HT synthesis with para-chlorophenylalanine (pCPA) had only minimal effects on withdrawal jumping per se; the attenuating effects of 8-OH-DPAT and RU 24969 were not altered in pCPA-pretreated animals. The effects of RU 24969 were blocked by (-)-pindolol and, stereoselectively, by (-)-SDZ 21-009. (-)-Pindolol neither influenced the action of 8-OH-DPAT nor showed any effect per se. The actions of 8-OH-DPAT and buspirone, but not of RU 24969 and idazoxan, were blocked by the 5-HT1A receptor antagonist, spiroperidol. Similarly, both haloperidol and prazosin prevented the attenuating action of 8-OH-DPAT but did not interfere with the action of RU 24969. We conclude that the actions of 8-OH-DPAT and RU 24969 are mediated by postsynaptic receptors. The 5-HT1B receptor appears to mediate the attenuating action of RU 24969; the exact mechanism of action of 8-OH-DPAT remains open but activation of an alpha 1-adrenoceptor is implicated.
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PMID:5-HT1 receptor agonists attenuate the naloxone-induced jumping behaviour in morphine-dependent mice. 256 95

1. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and flesinoxan, agents which show high affinity and selectivity for 5-HT1A receptors, were administered intravenously in doses of 0.003 to 0.1 and 0.01 to 0.3 mg kg-1 respectively to 5 rabbits each. Their effects were compared with those of the centrally acting agent and alpha 2-adrenoceptor agonist, guanfacine, 0.01-0.3 mg kg-1, administered to a group of 5 rabbits. Five further rabbits were used as controls and treated with the vehicle of the active agents. 2. Both flesinoxan and 8-OH-DPAT induced similar systemic and regional haemodynamic changes. Both lowered mean arterial pressure and heart rate. The principal blood pressure lowering mechanism was vasodilatation; cardiac output changed minimally despite the falls in heart rate and myocardial contractile force. 3. With guanfacine the maximal fall of blood pressure was comparable to that obtained with the 5-HT1A receptor ligands; however, in contrast to the latter, the dose-response curve was U-shaped, the highest dose eliciting a pressor effect with reversal of the vasodilatation. 4. Widespread peripheral vasodilatation was found with all the agents in the splanchnic circulation and also in the brain and skeletal muscle. A weak tendency towards vasodilatation was found in the kidneys where the dose-response curve was bell-shaped for guanfacine. 5. This spectrum of activity is different from that of peripheral vasodilators, such as calcium antagonists, potassium channel activating agents or hydralazine; it is, however, consistent with the putative mechanism of action of these compounds to reduce peripheral sympathetic tone by a central mechanism of action.
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PMID:8-OH-DPAT, flesinoxan and guanfacine: systemic and regional haemodynamic effects of centrally acting antihypertensive agents in anaesthetized rabbits. 256 44

The effects of 5-hydroxytryptamine (5-HT) on the release of gamma-aminobutyric acid (GABA) were examined in the longitudinal muscle-myenteric plexus (LM-MP) preparation of guinea-pig ileum. 5-HT increased the spontaneous release and inhibited the electrically-evoked release of [3H]-GABA. The 5-HT-evoked release was Ca2+-dependent and tetrodotoxin-sensitive, and was antagonized by (3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205-930), but not by methysergide and ketanserin. The inhibitory effect of 5-HT was antagonized by methysergide, but not by ketanserin and ICS 205-930. 8-Hydroxy-2-(di-n-propylamino)tetralin mimicked the inhibitory effect of 5-HT. Thus, 5-HT may exert an excitatory effect on the enteric GABAergic neurone via the 5-HT3 receptor and an inhibitory effect via the 5-HT1A receptor.
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PMID:Dual effects of 5-hydroxytryptamine on the release of gamma-aminobutyric acid from myenteric neurones of the guinea-pig ileum. 281 20

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) has effects both characteristic of a serotonin (5-hydroxytryptamine; 5-HT) agonist and antagonist. To investigate the mechanism(s) of action of 8-OHDPAT in vivo, rats were trained to discriminate 8-OHDPAT (0.4 mg/kg) from saline and given various neuroactive compounds during substitution test sessions. Of the 5-HT agonists tested, d-lysergic acid diethylamide, 5-methoxy-n,n-dimethyltryptamine, quipazine, Ru 24969 and 1-(m-trifluoromethylphenyl) piperazine did not mimic the training drug; the dopamine agonists apomorphine and SKF 38393 as well as the alpha 2-adrenoceptor agonist clonidine engendered predominantly saline-lever responding. However, the novel anxiolytics buspirone and ipsapirone as well as the ergot derivative lisuride substituted completely for 8-OHDPAT. In combination tests, 5-HT (ketanserin, metergoline, methysergide, pirenperone), dopamine (haloperidol) and norepinephrine antagonists (prazosin, propranolol) failed to attenuate the 8-OHDPAT cue. The similar stimulus properties of 8-OHDPAT and the novel anxiolytics (buspirone, ipsapirone) are mirrored by the common abilities of these agents to selectively inhibit 5-HT1A binding and release punished responding. Thus, the subpopulation of 5-HT1A receptors may mediate the behavioral effects of these compounds in animals and, in turn, the anxiolytic effects of buspirone and ipsapirone in humans. Although not primarily selective for 5-HT, lisuride may also mimic 8-OHDPAT by direct or indirect stimulation of 5-HT1A receptors.
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PMID:Discriminative stimulus properties of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT): implications for understanding the actions of novel anxiolytics. 288 35

Serotonergic (5-HT) neuronal pathways regulate the release of adrenocorticotropin hormone (ACTH) from the pituitary gland probably through the action of hypothalamic corticotropin-releasing hormone (CRH). 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist, dose dependently (0.016-3 mg/kg s.c.) increased rat plasma ACTH concentration. This response was blocked stereoselectively by (-)-pindolol, known to have 5-HT1 antagonist properties, but not by (+)-pindolol, beta 1-, beta 2- or alpha 1-adrenoceptor, dopamine, muscarinic, 5-HT2 or 5-HT3 receptor antagonists. Similar increases of plasma ACTH were induced by other 5-HT1A receptor ligands (buspirone, ipsapirone and gepirone). These results suggest that activation of the 5-HT1A receptor induces the secretion of ACTH from the rat pituitary gland.
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PMID:Activation of the 5-HT1A receptor subtype increases rat plasma ACTH concentration. 289 20


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