Inositol trisphosphate/Ca2+ as messengers of bradykinin B2 and muscarinic acetylcholine ml-m4 receptors in neuroblastoma-derived hybrid cells

Abstract

Neuroblastoma × glioma hybrid NG108-15 and neuroblastoma × fibroblast hybrid NL308 cells possess endogenous bradykinin B₂ receptors and m4 muscarinic acetylcholine receptors (mAChRs), which couple to phospholipase C and adenylate cyclase, respectively. Four genetic subtypes of mAChRs differed in their effects when stimulated in NG108-15 and NL308 cells overexpressing mAChRs. Broadly speaking, the principal effects fell into two categories: the odd-numbered receptors (ml and m3) activated phospholipase C and increased inositol trisphosphate/Ca²⁺, as bradykinin did, whereas the even-numbered receptors (m2 and m4) inhibited adenylate cyclase via a pertussis toxin (PTx)-sensitive G-protein in NG108-15 cells. But all four types of NL308 cells overexpressing each m1, 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 effectors showed a comparable dichotomy in NG108-15 cells, while cross-activation occurred in NL308 cells.