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)

Bovine pulmonary artery smooth muscle (SM) cells express a novel 5-hydroxytryptamine (5-HT) (5-HT4-like) receptor coupled to cAMP accumulation. cAMP radioimmunoassay established the agonist and antagonist profiles of this receptor. 5-HT (EC50 = 91 +/- 33 nM) and 5-methoxytryptamine were equipotent at the SM cell 5-HT receptor and both were more potent than 5-carboxamidotryptamine. Other tryptamine derivatives were less potent but remained full agonists. These findings are consistent with previous reports regarding 5-HT4 and 5-HT4-like receptors in the central nervous system. The most potent antagonists were the antidepressant compounds nortriptyline (IC50 = 177 +/- 153 nM) and zimelidine (IC50 = 202 +/- 101 nM). The 5-HT3 and 5-HT4 antagonist 3-tropanyl-indole-3-carboxylate (ICS 205-930) was also a competitive antagonist at this 5-HT4-like receptor (pA2 = 6.3). Antagonist affinities differed slightly at the SM cell receptor, compared with other 5-HT4 and 5-HT4-like receptors in the central nervous system. Nonetheless, the SM cell 5-HT4-like receptor displayed the same differential antagonist potencies as reported for these other receptors (ICS 205-930 > MDL 72222 and mianserin > ketanserin). 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was the most potent agonist for this 5-HT4-like receptor (EC50 = 6.4 +/- 3.4 nM). 8-OH-DPAT-induced cAMP accumulation could be blocked by ICS 205-930 but not by the 5-HT1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-pthalimido)butyl]piperazine hydrobromide, distinguishing the SM cell 5-HT receptor from 5-HT1A receptors. The mechanism of 5-HT-stimulated cAMP production was also investigated. First, GTP augmented basal and 5-HT-stimulated cAMP accumulation. Second, antisera to the carboxyl terminus of the alpha subunit of Gs, attenuated 5-HT-mediated adenylate cyclase activation. This established that 5-HT-stimulated cAMP accumulation in SM cells required GS. These findings suggest that SM cells express a novel 5-HT4-like receptor positively coupled to adenylate cyclase. An unexpected finding was that 8-OH-DPAT is a potent partial agonist. These studies suggest that there may be heterogeneity among 5-HT4-like receptors.
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PMID:8-hydroxy-2-(di-n-propylamino)tetralin-responsive 5-hydroxytryptamine4-like receptor expressed in bovine pulmonary artery smooth muscle cells. 133 64

1. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) dose-dependently induced hypothermia in mice. 2. The 5-HT1A receptor partial agonists, buspirone, gepirone and ipsapirone, also dose-dependently induced hypothermia. 3. The 8-OH-DPAT temperature response was antagonized by the 5-HT1 receptor antagonists quipazine (2 mg kg-1, i.p.), (+/-)-propranolol (10 mg kg-1, i.p.). (+/-)-pindolol (5 mg kg-1, i.p.), spiroxatrine (0.5 mg kg-1, i.p.) and metitepine (0.05 mg kg-1, i.p.), but not by 5-HT2 (ketanserin) or 5-HT3 (MDL 72222, GR 38032F) receptor antagonists. 4. The response was also antagonized by the dopamine D2 receptor antagonists, haloperidol and BRL 34778. No other catecholamine or muscarinic receptors were involved in mediating the response. 5. Destruction of 5-hydroxytryptamine (5-HT)-containing neurones with the neurotoxin, 5,7-dihydroxytryptamine (75 micrograms, i.c.v.), abolished the response to 8-OH-DPAT indicating that the 5-HT1A receptors involved were located on 5-HT neurones. 6. Chronic antidepressant treatment down-regulated this 8-OH-DPAT response. In addition, chronic administration of anxiolytics and neuroleptics was also effective in this respect. Down-regulation was also observed following repeated administration of 8-OH-DPAT (0.5 mg kg-1, s.c.), (+/-)-pindolol (10 mg kg-1, i.p.) and ketanserin (0.5 mg kg-1, i.p.). 7. In conclusion, these data confirm that 8-OH-DPAT-induced hypothermia is mediated by 5-HT1A autoreceptors. They also indicate that the response involves D2 receptors.The present study also shows that a wide range of antidepressant drugs down-regulate this response although this property is not restricted to antidepressant treatments. Therefore, care should be exercised when interpreting data from this paradigm.
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PMID:Characterization of 8-OH-DPAT-induced hypothermia in mice as a 5-HT1A autoreceptor response and its evaluation as a model to selectively identify antidepressants. 142 68

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a potent 5-HT1A receptor agonist, was infused in the dorsal hippocampus of rats and its effect on acquisition and performance of a 2-platform spatial discrimination task was studied using a water maze. The infusion (0.5 microliter/min) of 2 but not 0.4 microgram 8-OH-DPAT in the CA1 region of the dorsal hippocampus impaired rats' accuracy with no effect on latency (except day 3). At 5 micrograms 8-OH-DPAT impaired rats' accuracy and significantly increased choice latencies from day 2 to day 5 of the training period. The dose of 2 micrograms significantly increased the errors of omissions on the first day of training and animals which had received 5 micrograms 8-OH-DPAT made significantly more errors of omission on the first and second days of training. Intrahippocampal administration of 1 microgram spiroxatrine, a 5-HT1A receptor antagonist, antagonized the effect of 5 micrograms 8-OH-DPAT on accuracy and choice latency with no significant effect on the errors of omission on days 1 and 2 of training. Infusion of 2 and 5 micrograms 8-OH-DPAT in the dorsal hippocampus also impaired accuracy in well-trained rats. The results suggest that stimulation of 5-HT1A receptors in the CA1 region of the dorsal hippocampus causes an impairment of spatial discrimination in rats.
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PMID:Stimulation of 5-HT1A receptors in the dorsal hippocampus impairs acquisition and performance of a spatial task in a water maze. 146 58

This study was designed to determine the subtypes of 5-HT receptors present in bovine large coronary arteries and to characterize the response mediated by each subtype of receptor. Concentration-response relationships for 8-hydroxy-2-(di-n-propylamino)-tetralin (5-HT1A agonist) (0.3-100 microM), CGS-12066B maleate (5-HT1B agonist) (0.01-30 microM), alpha-methylserotonin maleate (5-HT2 agonist) (0.01-30 microM), 1-(m-chlorophenyl)-biguanide (5-HT3 agonist) (0.1-100 microM) and serotonin (0.1-300 microM) were studied in vitro using 2-mm segments of bovine proximal left anterior descending coronary artery. Each segmental ring was mounted in a 70-ml tissue bath for the measurement of isometric tension. 8-Hydroxy-2-(di-n-propylamino)-tetralin (10-100 microM), alpha-methylserotonin maleate (0.01-30 microM) and serotonin (0.1-300 microM) induced endothelium-independent contraction, whereas CGS-12066B maleate and 1-(m-chlorophenyl)-biguanide had no effect in this species. Contractions induced by 8-hydroxy-2-(di-n-propylamino)-tetralin or alpha-methylserotonin maleate were attenuated by pretreatment with S(-)propranolol (2.6 microM), a relatively selective 5-HT1A and 5-HT1B receptor antagonist, and ketanserin (0.3 microM), a selective 5-HT2 receptor antagonist, respectively. Pretreatment with S(-)propranolol or ketanserin also attenuated serotonin-induced contraction, demonstrating that serotonin mediates contraction through both 5-HT1A and 5-HT2 receptors in bovine large coronary arteries.
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PMID:Characterization of 5-hydroxytryptamine receptors in bovine coronary arteries. 153 67

8-Hydroxy-(di-n-propylamino)tetralin (8-OH-DPAT) has antidepressant-like effects in rats and selectively reduces presynaptic 5-HT1A function a day after administration. In the present study, the effect of 8-OH-DPAT (1 mg/kg s.c.) pretreatment on presynaptic (raphe nuclei) and postsynaptic (frontal cortex and hippocampus) [3H]8-OH-DPAT binding was studied. Bmax values were markedly reduced in the raphe, but not in the hippocampus and frontal cortex. Kd values were unchanged. Electrical stimulation of the dorsal raphe (300 microA, 1 ms, 20 Hz, 30 min) significantly increased 5-hydroxyindoleacetic acid in the frontal cortex, but not in the amygdala or the nucleus accumbens and caused smaller increases in the rest of the brain. The increase in the frontal cortex was significantly potentiated one day after giving 8-OH-DPAT. These results confirm the ability of 8-OH-DPAT to desensitise presynaptic 5-HT1A receptors and suggest that this may lead to a loss of feedback control so that, on neuronal stimulation, the increase of 5-HT function is enhanced. This effect may underlie the antidepressant-like action of 8-OH-DPAT pretreatment, i.e. its ability to oppose restraint-induced defects in locomotion on placement in an open field one day later. A requirement of presynaptic 5-HT for this behavioural effect is consistent with its prevention by the 5-HT synthesis inhibitor parachlorophenylalanine.
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PMID:A single dose of 8-OH-DPAT reduces raphe binding of [3H]8-OH-DPAT and increases the effect of raphe stimulation on 5-HT metabolism. 169 12

The effect of the serotonergic receptor agonist 1-(m-trifluoromethylphenyl)piperazine (TFMPP) was studied on the K(+)-evoked [3H]acetylcholine [( 3H]ACh) release from guinea pig hippocampal synaptosomes loaded with [3H]choline. TFMPP (5-1,000 microM) inhibited the evoked ACh release in a dose-dependent manner (IC50 = 81.8 microM). The inhibitory effect of TFMPP was mimicked by CGS-12066B (10, 30, and 100 microM), a 5-hydroxytryptamine1B (5-HT1B)/5-HT1D receptor agonist; 1-(m-chlorophenyl)piperazine (100 microM), a 5-HT1C/5-HT1B receptor agonist; and 5-carboxamidotryptamine (10 microM), a nonselective 5-HT1 receptor agonist. 8-Hydroxy-2-(di-n-propylamino)tetralin (10 and 100 microM), a 5-HT1A receptor agonist, and quipazine (10 and 100 microM), a 5-HT2 receptor agonist, did not have any significant effect. Serotonergic antagonists, such as dihydroergotamine (0.1 and 1 microM), metergoline (0.1 microM), methysergide (0.5 and 1 microM), or yohimbine (1 and 10 microM), blocked the TFMPP effect dose-dependently. In contrast, methiotepine (0.3 and 1 microM), propranolol (1 microM), ketanserin (0.1 microM), mesulergine (0.1 microM), ICS 205930 (0.1 and 1 microM), and spiroperidol (1 and 7 microM) did not affect the TFMPP-induced inhibition of the evoked ACh release. These data suggest that, in guinea pig hippocampus, the K(+)-evoked ACh release is modulated by a 5-HT1 receptor distinct from the 5-HT1A, 5-HT1B, and 5-HT1C subtypes.
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PMID:The inhibitory effect of trifluoromethylphenylpiperazine on [3H]acetylcholine release in guinea pig hippocampal synaptosomes is mediated by a 5-hydroxytryptamine1 receptor distinct from 1A, 1B, and 1C subtypes. 182 81

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) is a 5-HT1A receptor-selective agonist that has recently been reported to trigger adrenal catecholamine release and hyperglycemia. The aim of this study was to analyze in the conscious rat whether the 5-HT1A receptor subtype is involved in these effects. 8-OH-DPAT (0.1-1 mg/kg, i.v.) evoked dose-dependent increases in plasma adrenaline and glucose concentrations. Increases in plasma adrenaline levels peaked 5 min after administration of 8-OH-DPAT; in contrast, plasma glucose levels rose throughout the 20 min period of analysis. Prior administration of (-)pindolol, a beta-adrenoceptor antagonist that blocks 5-HT1A receptors, markedly diminished the rise in plasma adrenaline levels and abolished the hyperglycemia triggered by 8-OH-DPAT. On the other hand, neither the selective beta 1-adrenoceptor antagonist, betaxolol, the selective beta 2-adrenoceptor antagonist, ICI 118.551, nor the 5-HT2 receptor antagonist, ketanserin, affected 8-OH-DPAT-induced increases in plasma adrenaline levels. In addition, except for ICI 118.551 pretreatment, which delayed the hyperglycemic effect of 8-OH-DPAT, none of these antagonists affected the rise in glycaemia evoked by 8-OH-DPAT. The data suggest that the adrenaline-releasing and a major part of the hyperglycemic effects of 8-OH-DPAT are mediated by activation of 5-HT1A receptors.
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PMID:Evidence that 5-HT1A receptors are involved in the adrenaline-releasing effects of 8-OH-DPAT in the conscious rat. 197 Jun 16

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) dose dependently increased cortical acetylcholine (ACh) release and the body temperature of freely moving guinea pigs. Moreover, it evoked an electroencephalographic (EEG) arousal reaction in phenobarbital-pretreated animals. 8-OH-DPAT was about 10 times less effective in increasing cortical ACh release in the rat than in the guinea pig, and did not modify the phenobarbital-synchronized EEG but dose dependently decreased body temperature. The possibility that 5-HT1A receptors play different roles, depending on the animal species, is discussed.
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PMID:Different effects of 8-OH-DPAT, a 5-HT1A receptor agonist, on cortical acetylcholine release, electrocortigram and body temperature in guinea pigs and rats. 213 87

1. Intracellular recordings were made from neurones of the nucleus prepositus hypoglossi (PH) in slices of guinea-pig brain. Focal stimulation evoked an inhibitory postsynaptic potential (IPSP) that was typically 10-25 mV in amplitude and 1 s in duration. The IPSP reversal potential showed a Nernstian dependence on the external potassium concentration ([K+]o). 2. Spiperone blocked the IPSP with an IC50 of 40 nM, while ketanserin and (-)sulpiride had no effect. Cocaine (1 microM) prolonged the IPSP half-duration by 157%, and increased the amplitude by 28%. 3. 5-Hydroxytryptamine (5-HT, serotonin) hyperpolarized PH cells with an EC50 of 8.5 microM in control, and 135 nM in cocaine (10 microM). 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) also hyperpolarized PH cells with an EC50 of 16 nM, although the maximal effect was only 81% of the maximum 5-HT hyperpolarization. Spiperone produced a parallel, right shift of the 5-HT concentration-response curve; Schild analysis gave a Kd of 10 nM. Application of 5-HT to neurones voltage-clamped near their resting potential (about -55 mV) caused an outward current and an increase in membrane conductance. 4. The amplitude of the IPSP was reversibly decreased by non-hyperpolarizing concentrations of 5-HT and by the 5-HT1 receptor agonists 1-(m-trifluoromethylphenyl)piperazine (TFMPP) and 1-(3-chlorophenyl)piperazine (mCPP). The IC50 values for the latter two compounds were 50 nM and 1.5 microM, respectively; the maximal effect was a 90% inhibition. Neither compound affected the membrane potential nor changed the hyperpolarization induced by 5-HT. Quipizine competitively antagonized TFMPP with an estimated Kd of 165 nM. 5. When trains of stimuli were applied, an inhibition of the IPSP was observed following the first stimulus. At a frequency of 1 Hz, the inhibition was approximately 75%. This frequency-dependent 'run-down' of the IPSP was markedly attenuated by pre-treatment with TFMPP (1 microM). 6. It is concluded that the IPSP in PH cells is caused by 5-HT acting on 5-HT1A receptors to activate a potassium conductance. The release of 5-HT can be inhibited by activation of a presynaptic 5-HT1D receptor. This presynaptic receptor appears to be at least partly responsible for the run-down phenomenon, and may be involved in the physiological regulation of 5-HT synaptic transmission.
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PMID:Serotonin-mediated inhibitory postsynaptic potential in guinea-pig prepositus hypoglossi and feedback inhibition by serotonin. 214 Oct 79

Selective activation of the 5-HT1A receptor induces lower lip retraction (LLR) in rats. 8-Hydroxy-dipropylamino tetralin (8-OH-DPAT)-induced LLR could not be antagonised by the 5-HT antagonists methysergide, metergoline or mesulergine. In fact, some 5-HT antagonists induced LLR. However, 8-OH-DPAT-induced LLR could be antagonised by pindolol, spiperone, spiroxatrine and NAN-190, but not by the beta 1-adrenoceptor antagonist metoprolol, the beta 2-adrenoceptor antagonist butoxamine or the dopamine antagonist haloperidol. This antagonism was competitive as the dose-response curve of 8-OH-DPAT was shifted to the right. Pindolol, spiperone, spiroxatrine and NAN-190 all have a high affinity for the 5-HT1A receptor. This indicates that blockade of 8-OH-DPAT-induced LLR is only possible by selective blockade of 5-HT1A receptors. A possible mechanism of action is discussed. The increased defecation induced by 8-OH-DPAT could be antagonised by pindolol and NAN-190. The effect of spiroxatrine and haloperidol on the 8-OH-DPAT-induced increase in defecation was bimodal: an increase after a low and a decrease after a high dose of 8-OH-DPAT. Metoprolol and butoxamine had no effect on the 8-OH-DPAT-induced increase in defecation, thereby excluding an influence of beta-adrenoceptors.
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PMID:Antagonism of 8-OH-DPAT-induced behaviour in rats. 214 26


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