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)

Phosphatidylinositol (Ptdlns) turnover has been studied in the primary culture of granule cells dissociated from the cerebellum of postnatal rat. Addition of serotonin (5-hydroxytryptamine, 5-HT) caused an increase (300-600% of control) of [3H]inositol monophosphate (IP1) accumulation in the presence of LiCl in cells prelabeled with [3H]myo-inositol. The EC50 and saturation concentrations of 5-HT were about 0.1 and 10 microM respectively. Some nonselective 5-HT receptor agonists, MK212, 5-methoxytryptamine, tryptamine and quipazine, were capable of stimulating IP1 accumulation; a selective 5-HT1A receptor agonist, 8-OH-DPAT, was ineffective. The 5-HT-induced response was potently blocked by several 5-HT2 receptor antagonists such as ketanserin, mianserin, spiroperidol and pyzotyline. The 5-HT-induced accumulation was dependent on the culturing time of granule cells with the maximal response seen in an 8-day culture. Norepinephrine (NE) also promoted an increased IP1 accumulation (300% of the control) with an EC50 of about 1 microM, while prazosin inhibited this NE-induced response with a Ki of about 0.2 nM. The responses induced by NE and 5-HT appeared to be additive. In addition, histamine in a dose-dependent manner enhanced the accumulation by about 100%; this histamine effect was blocked by triprolidine, an H1 receptor antagonist, but not by cimetidine, an H2 receptor antagonist. These results suggest that 5-HT, NE and histamine could be part of the neurotransmitter substances present in mossy fibers or other afferent nerve endings which innervate granule cells in vivo and that Ptdlns turnover regulated by their selective receptors on granule cells may play a role in modulating the excitatory function of these neurons.
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PMID:Serotonergic, adrenergic and histaminergic receptors coupled to phospholipase C in cultured cerebellar granule cells of rats. 303 21

1. We studied the effects of tandospirone, a novel serotonin (5-HT)1A receptor-related anxiolytic, on the intracellular second messenger systems and neurotransmitter release. 2. Tandospirone inhibited forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes by activation of 5-HT1A receptors and had high efficacy comparable to 5-HT1A receptor agonists such as 5-HT and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 3. Tandospirone suppressed carbachol-stimulated phosphatidyl-inositol metabolism (PI response), which was shown to be a 5-HT1A receptor-mediated event. 4. Tandospirone did not affect the release of 5-HT, norepinephrine (NE), dopamine (DA) and acetylcholine (ACh) from rat brain slice preparations. 5. These findings suggested that tandospirone shows high agonistic efficacy on the postsynaptic 5-HT1A receptors but does not affect the presynaptic autoreceptors located on nerve endings. The modulation of the second messenger system via postsynaptic 5-HT1A receptors might be involved in the anxiolytic efficacy of tandospirone.
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PMID:Effects of tandospirone on second messenger systems and neurotransmitter release in the rat brain. 874 67