INOSITOL TRISPHOSPHATE CA2+ AS MESSENGERS OF BRADYKININ B-2 AND MUSCARINIC ACETYLCHOLINE M1-M4 RECEPTORS IN NEUROBLASTOMA-DERIVED HYBRID-CELLS/

Neuroblastoma x glioma hybrid NG108-15 and neuroblastoma x fibroblast hybrid NL308 cells possess endogenous bradykinin B-2 receptors and m4 muscarinic acetylcholine receptors (mAChRs), which couple to phospholi pase C and adenylate cyclase, respectively. Four genetic subtypes of m AChRs differed in their effects when stimulated in NG108-15 and NL308 cells overexpressing mAChRs. Broadly speaking, the principal effects f ell into two categories: the odd-numbered receptors (m1 and m3) activa ted phospholipase C and increased inositol trisphosphate/Ca2+, as brad ykinin did, whereas the even-numbered receptors (m2 and m4) inhibited adenylate cyclase via a pertussis toxin (PTx)-sensitive G-protein in N G108-15 cells. But all four types of NL308 cells overexpressing each m 1, m2, m3 and m4 receptor activated phospholipase C, while keeping the PTx-sensitivity in m2/m4, but not in m1/m3 receptors. Coupling to ion channel effecters showed a comparable dichotomy in NG108-15 cells, wh ile cross-activation occurred in NL308 cells.