Tohda M, Imaizumi R, Sekiya A, Itoh N, Nomura Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences Hokkaido University, Sapporo, Japan.
Biol Pharm Bull. 1995 Aug;18(8):1072-5. doi: 10.1248/bpb.18.1072.
Characterization of the serotonin-induced increase in guanosine 3',5'-cyclic monophosphate (cyclic GMP) was investigated and compared with that induced by atrial natriuretic peptide (ANP) in NG108-15 cells. The cyclic GMP formed by serotonin or ANP was transported in a similar manner to the extracellular medium, although the cyclic GMP formed by bradykinin was not. Serotonin and ANP raised cyclic GMP additively. Serotonin-induced cyclic GMP formation was completely inhibited by pretreatment with 100 nM 12-o-tetradecanoylphorbol 13-acetate (TPA), although that induced by ANP was only partially inhibited and the effects were blocked by pretreatment with staurosporin. In membrane preparations, ANP stimulated cyclic GMP formation in the presence of ATP, but serotonin did not. Serotonin-stimulated cyclic GMP formation was found to occur in neuroblastoma N18TG-2, but not in glioma C6Bu-1. These results suggest that a novel subtype of serotonin receptors (5-HTGC) which stimulates membrane-bound guanylyl cyclase, different from that stimulated by natriuretic peptide, may exist especially in neurons.
研究了血清素诱导的3',5'-环磷酸鸟苷（环鸟苷酸）增加的特性，并与心房利钠肽（ANP）在NG108-15细胞中诱导的情况进行了比较。血清素或ANP形成的环鸟苷酸以与细胞外介质相似的方式转运，而缓激肽形成的环鸟苷酸则不然。血清素和ANP对环鸟苷酸的升高具有相加作用。用100 nM 12-邻十四酰佛波醇13-乙酸酯（TPA）预处理可完全抑制血清素诱导的环鸟苷酸形成，而ANP诱导的环鸟苷酸形成仅被部分抑制，且这些作用可被星形孢菌素预处理阻断。在膜制剂中，ANP在ATP存在下刺激环鸟苷酸形成，而血清素则不能。发现血清素刺激的环鸟苷酸形成发生在神经母细胞瘤N18TG-2中，而在胶质瘤C6Bu-1中则不发生。这些结果表明，可能存在一种新型的血清素受体亚型（5-HTGC），它刺激膜结合鸟苷酸环化酶，与利钠肽刺激的受体不同，尤其存在于神经元中。
