title: Serotonin increases the production of inositol phosphates and mobilises calcium via the 5-HT2 receptor in A7r5 smooth muscle cells.
abstract: Serotonin (5-HT) induces inositol phosphate production and the efflux of 45Ca2+ in a smooth muscle cell line (A7r5) derived from rat aorta. These effects were pharmacologically characterised and compared to data obtained in radioligand binding studies performed with the 5-HT2 ligand [3H]ketanserin in rat brain cortex membranes. 5-HT causes in increase in the levels of inositol trisphosphate (InsP3), inositol bisphosphate (InsP2) and inositol phosphate (InsP1). InsP3 production was rapid and transient whereas InsP1 accumulated in a time and concentration dependent manner. The 5-HT stimulated InsP1 accumulation (pEC50 = 6.48) was potently and competitively inhibited by the 5-HT2 specific antagonists, pirenperone and ketanserin, whereas antagonists of other 5-HT receptors were active only at high concentrations. There was a significant correlation between inhibition of 5-HT stimulated InsP1 accumulation and 5-HT2 binding (r = 0.98, P = 0.0035). 5-HT stimulated the efflux of 45Ca2+ from preloaded cells with a pEC50 of 7.59. The rank order of potency for agonist induced Ca2+ efflux, 5-HT greater than alpha-methyl-5-HT greater than 1-methyl-5-HT greater than RU 24969 (5-methoxy-3[1,2,3,6,-tetrahydropyridin-4-yl]-1-H indole) greater than 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) greater than 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) greater than 5-CT (5-carboxamidotryptamine) is typical for a 5-HT2 receptor mediated event. The effect of 5-HT was competitively blocked by ketanserin (pA2 = 8.22).(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D001011:Aorta; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007650:Ketanserin; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013403:Sugar Phosphates / Q000096:biosynthesis*; D013997:Time Factors
chemical_list: D007295:Inositol Phosphates; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013403:Sugar Phosphates; D012701:Serotonin; D007650:Ketanserin; D002118:Calcium; C034177:pirenperone