Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase.

摘要: Serotonin modulates a wide range of physiological functions by activating multiple receptors, which are coupled to various effector systems. Using strategy based on amino acid sequence homology between 5-hydroxytryptamine (5-HT) we have isolated from mouse brain library cDNA encoding new 5-HT receptor, 5-HTx, that activates adenylate cyclase. Amino comparisons revealed the 5-HTx receptor was distant relative previously cloned with highest percentage (42%) being 5-HTdro1 Drosophila positively In COS-7 cells transiently expressing induced an increase in cAMP levels dose dependent and saturable (EC50 = 45 nM). Agonists displayed following rank order potencies: 5-carboxamidotryptamine > 5-methoxytryptamine RU 24969 8-hydroxy-2-(di-n-propylamino)tetralin. The most efficient antagonists inhibiting stimulatory effect were methysergide, methiothepin, mesulergine, metergoline, clozapine, ergotamine, (+)-butaclamol. Membranes single binding site for [3H]5-HT. potencies drugs displacing [3H]5-HT similar obtained experiments. pharmacological profile this does not correspond any classic subtypes. Expression mRNA brainstem lower forebrain, cerebellum, intestine, heart. might therefore 5-HT1-like receptors been shown induce relaxation porcine vena cava guinea pig ileum as well tachycardia cat high affinity neuroleptic agents such (+)-butaclamol clozapine suggests also play role certain neuropsychiatric disorders.