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

Abstract
Serotonin activates adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] of NCB(neuroblastoma-fetal Chinese hamster brain hybrid cell line)-20 neuroblastoma-brain hybrid cells with an activation constant of 530 nM, but has little or no effect on cellular cyclic[c]AMP or cGMP content of N1E-115 neuroblastoma (cloned from C1300 mouse neuroblastoma) or Ng(neuroblastoma glioma)108-15 hybrid cells. In homogenates of NCB-20 hybrid cells, LSD stimulates adenylate cyclase activity (Kact = 12 nM) and partially inhibits (Ki = 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 LSD. NCB-20 cells possess at least 2 spp. 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 cAMP or cGMP synthesis in the cell lines tested.