FUNCTIONAL-CHARACTERIZATION OF A 5-HT2 RECEPTOR CDNA CLONED FROM LYMNAEA-STAGNALIS

A G-protein-coupled receptor (5-HT2Lym) resembling members of the 5-HT 2 receptor subfamily was cloned from the mollusc Lymnaea stagnalis. Se rotonin induces a concentration-dependent increase in intracellular in ositol phosphates in HEK293 cells expressing this receptor (EC(50) = 1 14 nM). 5-HT2Lym differs from mammalian 5-HT2 receptors by the presenc e of a large amino-terminal region. This large domain appears to precl ude an adequate level of expression of 5-HT2Lym in HEK293. Therefore, we constructed a cDNA encoding an amino-terminally truncated receptor (Delta N-5-HT2Lym) that appeared to be much better expressed in HEK293 cells, Delta N-5-HT2Lym-expressing cells exhibit a serotonin-induced stimulation of phosphatidylinositol bisphosphate hydrolysis (EC(50) = 11.4 nM) and a high-affinity binding of the 5-HT2-selective antagonist [H-3]mesulergine (K-d = 4 nM). Inhibition of this binding by several 5-HT2 antagonists and agonists revealed a pharmacological profile most closely resembling those of 5HT(2Dro), 5-HT2B and 5-HT2C.