The Slow Cyclic GMP Increase Caused by Serotonin in NG108‐15 Cells Is Not Inhibited by Antagonists of Known Serotonin Receptors: Possible Existence of a New Receptor Subtype Coupled with Membrane‐Bound Guanylate Cyclase

Characterization of the serotonin (5‐HT>induced cyclic GMP (cGMP) elevation was investigated in comparison with bradykinin‐ and ANP‐induced elevations in NG108‐15 cells. At 20 s, l,2‐bis(2‐aminophenoxy)ethaae‐N,N,N′,N′‐tetraaoetic acid tetraacetoxymethyl ester (BAPTA‐AM, 100 μM), a membrane‐permeabilized Ca²⁺ chelator, or N‐monomethyl‐L‐arginine (NMMA, 300 μM), an inhibitor of L‐arginine‐derived nitric oxide (NO) synthesis, inhibited 5‐HT‐induced elevation by approximately 40%, and completely inhibited bradykinin‐induced response. Neither 5‐HT‐ nor ANP‐induced cGMP elevation at 10 rain was affected by BAPTAAM or NMMA. The cGMP elevated by 5‐HT as well as by ANP was effluxed to the extracellular medium. These results and our previous report suggest that 5‐HT stimulates two subtypes of 5‐HT receptors in NG108‐15: first, 5‐HT₃ subtype stimulating Ca²⁺‐sensitive cytosolic guanylate cyclaje through NO derived from L‐arginine and second, a probably novel 5‐HT receptor subtype involved in activation of membrane‐bound guanylate cyclase.