Adenylate cyclase and acetylcholine release regulated by separate serotonin receptors of somatic cell hybrids

Serotonin activates adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] of NCB-20 neuroblastoma-brain hybrid cells with an activation constant of 530 nM, but has little or no effect on cellular cyclic AMP or cyclic GMP content of N1E-115 neuroblastoma or NG108-15 hybrid cells. In homogenates of NCB-20 hybrid cells, lysergic acid diethylamide stimulates adenylate cyclase activity (K(act)=12 nM) and partially inhibits )K(i)=10 nM) the stimulation of adenylate cyclase activity by serotonin. No desensitization was detected of serotonin receptors coupled to adenylate cyclase. Serotonin also depolarizes NCB-20, NG108-15, and N1E-115 cells and increases acetylcholine release. Serotonin receptors mediating depolarizing responses desensitize rapidly and reversibly, and the depolarizing effects of serotonin are neither mimicked nor inhibited by lysergic acid diethylamide. These results indicate that: NCB-20 cells posses at least two species of serotonin receptors, which independently regulate cellular functions; activation of adenylate cyclase does not directly affect membrane potential or acetylcholine release; and serotonin-dependent cell depolarization does not affect cyclic AMP or cyclic GMP synthesis in the cell lines tested.