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 effects of urapidil, of the selective 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and of the alpha 2-adrenoceptor agonist clonidine on the in vivo rate of synthesis of 5-hydroxytryptamine (5-HT) were determined in rat brain cortex and hypothalamus. Urapidil (10 mg/kg), 8-OH-DPAT (0.3 mg/kg) or clonidine (0.3 mg/kg; all drugs i.p.) caused significant reductions in 5-HT synthesis rate. Pretreatment with the selective 5-HT1A receptor antagonist spiroxatrine (SPX; 1 mg/kg s.c.) or the nonselective 5-HT1 receptor antagonist metitepine (1 mg/kg i.p.) abolished the effects of urapidil and 8-OH-DPAT, but not of clonidine. The effects of urapidil and 8-OH-DPAT on mean arterial blood pressure (MAP) and heart rate (HR) of pentobarbital-anesthetized, normotensive rats were measured following stereotaxic microinjection into the B1/B3 cell region of the ventral medulla. The mean percentage decreases induced by urapidil (3 micrograms) and 8-OH-DPAT (0.2 micrograms) amounted to (MAP/HR) -13%/-6% and -19%/-25%, respectively. The following pretreatments markedly attenuated or prevented the effects of intramedullary injections of urapidil or 8-OH-DPAT: (a) SPX (1 mg/kg s.c., 60 min): (b) intracisternal injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 0.2 mg; 7-10 days); (c) bilateral injection of 5,7-DHT at the cervical level of the spinal cord (each side 5 micrograms; 7-10 days). The present results are compatible with an action of urapidil as agonist at central 5-HT1A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of urapidil and 8-OH-DPAT on brain 5-HT turnover and blood pressure in rats. 170 89

Activity in central sympathetic pathways can be modified by stimulating central alpha 2-adrenoceptors, e.g., with clonidine, or, more recently, by stimulating central 5-hydroxytryptamine (5-HT1A) receptors. Stimulation of 5-HT1A receptors causes central sympathoinhibition and an increase in cardiac vagal drive, which results in a profound fall in blood pressure. However, the central sympathoinhibition observed with 5-HT1A agonists such as 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] is not uniform for all regional sympathetic outflows, renal outflow being the most sensitive. The classical centrally acting antihypertensive drugs, the alpha 2-adrenoceptor agonists, also cause differential sympathoinhibition, but cardiac rather than renal nerve activity is the most sensitive. Now, if a 5-HT1A agonist is combined with an alpha 1-adrenoceptor antagonist, e.g., urapidil, then uniform central sympathoinhibition is observed. 5-HT1A agonists also differ from alpha 2-adrenoceptor agonists in that they increase central vagal drive. Further, 5-HT-containing boutons have been shown to make synaptic contact with cardiac vagal motoneurons (CVMs), and there is also a high density of 5-HT1A binding in the brain nuclei containing these CVMs. This suggests that there is an excitatory 5-HT-containing pathway that innervates CVMs and involves the activation of 5-HT1A receptors. In this respect, cardiopulmonary afferent fiber activation of CVMs is blocked by central administration of 5-HT1A receptor antagonists. In conclusion, 5-HT1A receptors are important in the patterning of sympathetic outflow by central cardiovascular pathways and are involved in the central control of parasympathetic outflow, at least to the heart.
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PMID:Influence of 5-HT1A receptor agonists on sympathetic and parasympathetic nerve activity. 170 90

The effects of the alpha 2-adrenoceptor antagonist idazoxan on 5-hydroxytryptamine (5-HT) neuronal firing and release have been investigated. Idazoxan, administered i.v. (10 micrograms/kg and 0.5 mg/kg) increased dorsal raphe nucleus (DRN)-5-HT neuronal firing rate in a dose-dependent fashion. At the higher dose, a voltammetric study revealed increases in extracellular 5-HT and 5-hydroxyindole acetic acid (5-HIAA) levels, there was no effect with the lower dose. Intra-raphe administration of idazoxan (1 ng) also elevated the firing rate of 5-HT neurones in the dorsal raphe, suggesting that idazoxan may produce the increase in firing by a direct effect in the DRN. However, microiontophoretic application of idazoxan did not increase the firing rate of 5-HT neurones in the DRN. Thus the increase in the firing rate of 5-HT neurones in the DRN observed with systemic and local administration of idazoxan is probably not due to a direct action of idazoxan on the 5-HT neurone. Possibly the idazoxan acted at alpha 2-adrenoceptors located on noradrenergic terminals thus stimulating noradrenaline release and consequently increased 5-HT activity. Chronic administration of idazoxan (0.8 mg/kg per h for 14 days), using osmotic mini-pumps, caused an elevation in basal firing rate and an attenuation of the inhibitory response of DRN 5-HT neurones to the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) (10 micrograms/kg i.v.). This finding suggests that chronic infusion with idazoxan leads to desensitisation of the 5-HT1A somatodendritic autoreceptor.
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PMID:Effects of idazoxan on dorsal raphe 5-hydroxytryptamine neuronal function. 171 Sep 90

Incoming serotonergic fibres are known to make direct synaptic contact with dopamine-containing neurones in the substantia nigra pars compacta (SNc). However, the effects of 5-HT (5-hydroxytryptamine) on these cells have not been thoroughly investigated. In the present study we show that application of 10-50 microM 5-HT increases the firing frequency of SNc neurones in-vitro, and produces inward rectification in a voltage region negative to -50mV. This effect is sensitive to extracellular Cs+, but not to Ba2+, and has similar properties as the intrinsic inward rectifier current, Ih. Antagonists of the 5-HT1A and 5-HT2 receptors were inefficacious. It is concluded that 5-HT excites SNc neurones via an enhancement of the conductance underlying Ih.
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PMID:Excitation of substantia nigra pars compacta neurones by 5-hydroxy-tryptamine in-vitro. 171 45

The effects of the 5-hydroxytryptamine type-2 (5-HT2) receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and the 5-HT1A agonist (+)-8-hydroxy-2-(di-n-propylamino)-tetralin [(+)-8-OH-DPAT] on nociceptive responsiveness were compared in mice. Intrathecal administration of DOI (5-20 micrograms) produced a dose-dependent behavioural syndrome, consisting of biting or licking, directed towards the caudal part of the body and reciprocal hindlimb scratching. However, (+)-8-OH-DPAT (5-20 micrograms) did not produce the biting and scratching behaviour. The response to DOI (20 micrograms) was reversed by treatment with the substance P receptor antagonist, [D-Arg1, D-Trp7,9, Leu11]-SP (Spantide) (5 micrograms). The tail-flick reflex was markedly depressed 5-20 min after administration of (+)-8-OH-DPAT; DOI did not change the tail-flick reflex after 5 min but significantly inhibited the reflex response 10-20 min after injection. The data show that stimulation of 5-HT2 receptors, but not 5-HT1A receptors, induced a behavioural syndrome, which may reflect activation of nociceptive pathways. The tail-flick reflex was more markedly inhibited by stimulation of 5-HT1A than 5-HT2 receptors. Accordingly, 5-HT2 and 5-HT1A receptors seem to have a different function in the modulation of nociceptive responsiveness in the mouse.
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PMID:Different role of 5-HT1A and 5-HT2 receptors in spinal cord in the control of nociceptive responsiveness. 171 72

The affinity of a new serotonin (S) derivative, serotonin-O-carboxymethyl-glycyl-tyrosinamide (S-CM-GTNH2), for the various 5-hydroxytryptamine (5-HT)1 receptor subtypes was tested using quantitative autoradiography on rat and guinea pig brain sections. In the rat, S-CM-GTNH2 is 57 and 24 times more potent at 5-HT1B sites (IC50 = 28 nM) than at 5-HT1A (IC50 = 1600 nM) and 5-HT1C sites (IC50 = 670 nM), respectively. In the guinea pig, the affinity of S-CM-GTNH2 for 5-HT1D sites (IC50 = 67 nM) is 21 times higher than at 5-HT1A sites (IC50 = 1400 nM). S-CM-GTNH2 shows a low affinity (less than 10 microM) for 5-HT2 and 5-HT3 binding sites. This new ligand is therefore highly specific for 5-HT1B and 5-HT1D binding sites and can be used to further characterize the involvement of these subtypes in physiological studies focusing particularly on behavioral effects.
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PMID:Pharmacological characterization of serotonin-O-carboxymethyl-glycyl-tyrosinamide, a new selective indolic ligand for 5-hydroxytryptamine (5-HT)1B and 5-HT1D binding sites. 176 84

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

The cloned 5-HT1A receptor, stably expressed in HeLa cells, has been shown to mediate the effects of 5-hydroxytryptamine (5-HT) to inhibit cAMP formation and to stimulate the hydrolysis of phosphatidylinositol. Both responses were found to be pertussis toxin sensitive. We have examined these two responses in membranes derived from these cells and show that the 5-HT1A receptor can directly regulate the activity of adenylyl cyclase and phospholipase C in response to agonist. In order to examine whether the same or distinct guanine nucleotide-binding regulatory protein(s) (G protein) are involved in these two signal transduction pathways, we used anti-peptide antibodies recognizing the alpha-subunits of Gi1, Gi2, Gi3 as specific tools, since these pertussis toxin substrates are expressed in HeLa cells. These antibodies have previously been shown to prevent receptor-G protein coupling by binding to the regions of G proteins which are putatively involved in interaction with receptors. Our results indicate that the Gi proteins, but preferentially Gi3, mediate the effects of 5-HT both to inhibit adenylyl cyclase and to stimulate phospholipase C. These findings demonstrate that the same receptor interacting with the same G protein can regulate several distinct effector molecules.
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PMID:Dual coupling of the cloned 5-HT1A receptor to both adenylyl cyclase and phospholipase C is mediated via the same Gi protein. 178 5

Buspirone has been available in the United States for over four years for the treatment of anxiety. It was anticipated this drug would offer certain advantages over the established benzodiazepines. In contrast to diazepam, early studies found no evidence for the interaction of buspirone with GABAergic mechanisms. Behavioural, electrophysiological and receptor binding experiments gradually led to the idea that buspirone owes much of its anxiolytic activity to its ability to attenuate central 5-hydroxytryptamine neurotransmission. Specifically, it appears to act as an agonist at presynaptic 5-HT1A receptors, particularly in the raphe nuclei. Although buspirone also shows an affinity for dopamine D2 receptors, where it seems to behave as an antagonist, there is much doubt that this effect is related to its anxiolytic action. Even though buspirone and the benzodiazepines do not obviously share a common mode of action, the possibility is discussed that there is an underlying common mechanism of responsible for their antianxiety effects.
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PMID:Molecular basis of buspirone's anxiolytic action. 179 57

Intrathecal administration (ith) of 5-hydroxytryptamine (5-HT, 1.56, 3.125, 6.25 and 12.5 micrograms/10 microliters) to conscious rats produced a marked dose-dependent hypertensive effect without significant change in heart rate (HR). Ith administration of fluoxetine (10 micrograms/microliters), one of the presynaptic reuptake inhibitors of 5-HT, produced a marked increase in the mean arterial blood pressure (mABP). This effect could be prevented by a pretreatment with cinanserin (25 micrograms ith) as a blocker of 5-HT receptor. It was further observed that ith of 8-OH-DAPT (2.5, 5, 10 micrograms/10 microliters), a 5-HT1A receptor agonist, produced a dose-dependent increase of mABP and lowering of HR. However, ith of 5-HT3 receptor agonist 2-Methylserotonin (25, 50, 100 micrograms/10 microliters), decreased mABP markedly without change in HR. The results indicate that 5-HT in the spinal cord may extra hypertensive effect via 5-HT1A receptor and a hypotensive effect via 5-HT3 receptor. This gives a possible explanation about the conflicting reports concerning the effect of 5-HT in the central nervous system on blood pressure.
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PMID:[Cardiovascular reactions mediated by 5-HT1A and 5-HT3 receptors in the spinal cord of conscious rats]. 179 18


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