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)

Chronic injection of iminodipropionitrile (IDPN) to rats causes persistent motor abnormalities such as hyperactivity, lateral and vertical dyskinesia of the neck, and random circling. These behavioral changes are very similar to those observed after the acute administration of serotonin (5-HT) agonists in rodents. Moreover, some aspects of this syndrome are reproduced by stimulation of 5-HT1A receptors. The present quantitative autoradiographic study revealed a number of changes in 8-hydroxy-2-[di-n-propylamino-3H]tetralin (8-OH[3H]DPAT)-labeled 5-HT1A receptors in the brains of IDPN-treated rats. There were significant increases of 8-OH[3H]DPAT binding in the frontal cortex and in the caudate-putamen. In contrast, there were significant decreases in the interpeduncular nucleus, the pyramidal layer of the CA3 field of hippocampus, the superior colliculus and the pars reticulata of the substantia nigra. These results provide further evidence for the involvement of the 5-HT system in the development of the IDPN-induced dyskinetic syndrome.
Brain Res 1989 Dec 18
PMID:Regional changes in brain 5-HT1A serotonin receptors in the rat model of persistent spasmodic dyskinesias induced by iminodipropionitrile. 253 54

This study investigated the effects of the serotonin (5-HT)precursor 5-hydroxytryptophan (5-HTP) and the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on population responses in the dentate gyrus evoked by perforant path stimulation. Intraperitoneal injections of either compound into urethane anesthetized rats produced a substantial increase in the amplitude of the population spike, without affecting the granular layer population EPSP. These data suggest that enhanced serotonergic tone facilitates synaptic transmission between the entorhinal cortex and dentate gyrus in vivo, and that this facilitation may be mediated by a 5-HT1A receptor.
Brain Res 1989 Dec 25
PMID:Increased population spike amplitude in the dentate gyrus following systemic administration of 5-hydroxytryptophan or 8-hydroxy-2-(di-n-propylamino)tetralin. 253 47

The radiation inactivation technique has been used to estimate the molecular size of the 5-HT3 receptor binding site labelled by [3H]zacopride, in comparison with that of the 5-HT1A receptor binding site labelled by [3H]8-OH-DPAT, in rat cortical membranes. The calculated molecular weight of the 5-HT3 site: 35.4 +/- 2.2 kDa (mean +/- S.E.M., n = 4) was significantly less than that of the 5-HT1A site: 62.9 +/- 1.8 kDa (mean +/- S.E.M., n = 4) and of other 5-HT1 and 5-HT2 receptors of the G-protein coupled family. These data further support that the 5-HT3 receptor is not coupled to G-proteins in the rat brain.
Eur J Pharmacol 1989 Dec 05
PMID:Determination of the molecular size of the 5-HT3 receptor binding site by radiation inactivation. 253 81

In anaesthetised rats bilateral microinjection of 2 nmol 5-HT or the agonists 5-carboxyamidotryptamine (5-CT), 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) into nucleus paragigantocellularis lateralis produced a fall in blood pressure and heart rate, an increase in hindlimb vascular conductance but no significant change in renal conductance. In contrast, alpha-methyl-5-HT injected into the same region had no such effects. It is suggested that these cardiovascular effects are mediated by activation of 5-HT1A receptors. The possibility that there may be differences between species with respect to central 5-HT receptor-mediated cardiovascular effects is also discussed.
Neurosci Lett 1989 Dec 15
PMID:Systemic and regional haemodynamic responses to microinjection of 5-HT agonists in the rostral ventrolateral medulla in the rat. 253 33

The 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), induced a dose-dependent reduction in latency to withdraw the tail from noxious hot water (48 degrees C). However, a similar apparent 'hyperalgesia' was seen at a non-noxious temperature of 38 degrees C. Indeed, 8-OH-DPAT induced spontaneous 'tail-flicks' in the absence of external stimulation. This property was shared by lisuride and LSD, which also have high intrinsic activity at 5-HT1A sites. Agonists at other serotonin (5-HT) receptor types (5-HT1B, 5-HT1C, 5-HT2, 5-HT3) were inactive. Tail-flicks induced by 8-OH-DPAT could be antagonised by the 5-HT1 2 antagonist, methiothepin, but not by ritanserin or GR-38032F, which are antagonists at 5-HT2 and 5-HT3 sites, respectively. Ipsapirone and buspirone, partial 5-HT1A agonists, acted as antagonists. Further, BMY 7378, a proposed selective antagonist at 5-HT1A sites, also blocked the tail-flicks. Thus, the apparent 'hyperalgesia' induced by 8-OH-DPAT may reflect induction of spontaneous tail-flicks. These flicks appear to be mediated by 5-HT1A receptors and represent a novel model of 5-HT1A function in the rat.
Neurosci Lett 1989 Dec 15
PMID:Apparent hyperalgesic action of the 5-HT1A agonist, 8-OH-DPAT, in the rat reflects induction of spontaneous tail-flicks. 253 34

Imipramine, a tricyclic antidepressant, acts acutely to block the reuptake of serotonin (5-HT) and norepinephrine (NE). However, imipramine's action as an antidepressant takes several weeks to develop. This study investigated acute and chronic effects of imipramine on intracellularly-recorded responses mediated by 5-HT and beta-adrenergic receptors on pyramidal cells from area CA1 of rat hippocampal slices maintained in vitro. Addition of 10 microM imipramine in the perfusion medium sinistrally shifted the 5-HT1A concentration-response curve for membrane hyperpolarization and the 5-HT concentration-response curve for the reduction in the amplitude of the slow afterhyperpolarization (AHP) elicited by a train of action potentials. After two weeks of treatment with imipramine (10 mg/kg daily i.p. injections or s.c. osmotic mini-pumps) the responses to 5-HT were not altered. In contrast the concentration-response curve for the beta-adrenergic mediated reduction in AHP amplitude was significantly altered; there was a reduction in Emax and a log unit dextral shift in EC50. There was no change in the concentration-response curve for the beta-adrenergic mediated depolarization. These data are in agreement with previous biochemical results reporting a decrease in beta-adrenergic receptor mediated stimulation in adenylyl cyclase and down-regulation of beta-receptor in cortex and hippocampus. These findings suggest that a consequence of long-term imipramine treatment is a decrease in the augmentation of cell excitation normally produced by beta-adrenergic receptor stimulation.
Brain Res 1989 Dec 11
PMID:Imipramine alters beta-adrenergic, but not serotonergic, mediated responses in rat hippocampal pyramidal cells. 255 27

Regulation of phosphate uptake was studied in HeLa cell lines after transfection with DNA encoding the human 5-HT1A receptor. Phosphate uptake was saturable and greater than 90% sodium-dependent, with Vmax approximately 30-35% without changing Km. Treatment with 5-HT or the 5-HT1A-specific agonist 8-OH-2-(di-n-propylamino)1,2,3,4-tetrahydronaphthalene increased Vmax approximately 40% without affecting Km. This effect was blocked by pretreatment with the 5-HT1 antagonists, methiothepine and spiperone, or pertussis toxin. Surprisingly, the stimulation was not secondary to an inhibition of adenylyl cyclase because 5-HT stimulated phosphate uptake approximately 20% in the presence of 1 mM 8-Br-cAMP. Rather, the primary pathway linked to the stimulation of phosphate uptake involved activation of protein kinase C because (i) 5-HT measurably activated protein kinase C in these cells, (ii) activators of protein kinase C (phorbol esters and diacylglycerol analogues) stimulated phosphate uptake in these cells (iii) the half-maximal doses for 5-HT-induced phosphatidylinositol hydrolysis and stimulation of phosphate uptake were virtually equivalent, and both effects were equally sensitive to pertussis toxin, and (iv) the stimulation was markedly attenuated in cells made deficient in protein kinase C. These results demonstrate that the stimulation of phosphatidylinositol hydrolysis by the 5-HT1A receptor can generate physiologically measurable effects on cellular transport and suggest that such accessory pathways may play a prominent role in signal transduction.
J Biol Chem 1989 Dec 25
PMID:The human 5-HT1A receptor expressed in HeLa cells stimulates sodium-dependent phosphate uptake via protein kinase C. 255 47

MDL 73005EF has been recently described as a potent, highly selective 5-HT1A ligand. Although proposed to act predominantly as an antagonist (M. Hibert, A.K. Mir, G. Maghioros, P. Moser, D.N. Middlemiss, M.D. Trickleband and J.R. Fozard, 1988, The Pharmacological properties of MDL 73005EF: a potent and selective ligant at 5-HT1A receptors, Br. J. Pharmacol. 93, 2P), we have demonstrated that MDL 73005EF also acts as a highly efficacious partial agonist at the 5HT1A receptor, based on its ability to inhibit forskolin-stimulated adenylate cyclase in rat hippocampal membranes. Compared with two structurally related 5-HT1A partial agonists, the rank order of potency of MDL 73005EF in the FSC assay was comparable to affinity calculated by radioligand binding.
Eur J Pharmacol 1989 Dec 07
PMID:MDL 73005EF: partial agonist at the 5-HT1A receptor negatively linked to adenylate cyclase. 256 Apr 32

1. An investigation was carried out to determine whether the centrally acting hypotensive drugs whose mechanisms of action are due either to activation of 5-HT1A receptors (flesinoxan, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and urapidil--also an alpha 1-adrenoceptor antagonist) or to activation of alpha 2-adrenoceptors (clonidine and moxonidine) cause differential sympathoinhibition. 2. Cats were anaesthetized with alpha-chloralose and simultaneous recordings were made of whole cardiac, splanchnic and renal nerve activity, blood pressure and heart rate. Cumulative dose-response (i.v.) curves were constructed in separate experiments for the above hypotensive agents on these parameters. 3. Renal nerve activity was found to be more sensitive to the sympathoinhibitory action of flesinoxan and 8-OH-DPAT when compared with cardiac nerve activity, whereas the reverse was observed for clonidine and moxonidine, cardiac being more sensitive than renal nerve activity. Splanchnic nerve activity was similarly affected by all drugs. Furthermore at the highest dose, all drugs tended to cause complete inhibition in all regional sympathetic nerve outflows. 4. Urapidil differed from all the above hypotensive drugs in that it caused a similar degree of sympathoinhibition in all sympathetic outflows at all doses. It is suggested that this may be due to the ability of urapidil to block central alpha 1-adrenoceptors in addition to stimulation of 5-HT1A receptors.
Br J Pharmacol 1989 Dec
PMID:Evidence that different regional sympathetic outflows vary in their sensitivity to the sympathoinhibitory actions of putative 5-HT1A and alpha 2-adrenoceptor agonists in anaesthetized cats. 257 14

The effects of microinfusion of serotonin (5-HT) agents as well as glutamate and muscimol into the ventral tegmental area (VTA) on dopamine (DA) release in the ipsilateral nucleus accumbens (ACC) were investigated in freely moving rats, using a push-pull perfusion procedure. The baseline values for DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were approximately 0.24, 8.4, 2.1 and 2.7 pmol/15 min, respectively, in the push-pull perfusate of the ACC. When microinfused into the VTA, glutamate (0.74 microgram) significantly (p less than 0.05) increased the contents of DOPAC (110%) and HVA (90%) over baseline levels in the perfusate. On the other hand, 0.5 microgram muscimol (a gamma-amino-n-butyric acid, GABA, agonist) significantly, (p less than 0.05) decreased both DA (40%) and DOPAC (20%) levels relative to baseline values. Administration of 2 micrograms 5-HT into the VTA caused a significant (p less than 0.05) elevation in the perfusate levels of DOPAC (80%) and HVA (70%) over baseline values. A similar effect was obtained with a nonselective 5-HT1 agonist but not with a selective 5-HT1A agonist. The results suggest that 5-HT innervations in the VTA may have an excitatory action possibly via 5-HT1B rather than 5-HT1A receptors on the mesolimbic DA system projecting to the ACC and that this DA system may also be regulated by glutamatergic and GABAergic (via GABAA receptors) inputs.
Brain Res Bull 1989 Dec
PMID:Serotonin microinfusion into the ventral tegmental area increases accumbens dopamine release. 257 44


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