Endothelin receptors in rat cerebellum: activation of phosphoinositide hydrolysis is transduced by multiple G-proteins.

Induction of phosphoinositide hydrolysis in rat cerebellar slices by endothelins (ET-1 and ET-3) and sarafotoxins (SRTX-b and SRTX-c) was demonstrated by measurement of labelled inositol phosphate generation. Pertussis toxin (PT) enhanced the induction of phosphoinositide hydrolysis by all four peptides. The process seems to be mediated by at least two heterotrimeric G-proteins, the one sensitive and the other insensitive to PT. Measurement of the GTPase activity induced in this preparation indicated that phosphoinositide hydrolysis is stimulated via a functional coupling between the endothelin receptor of the ETB-R subtype and a PT-insensitive G-protein family, i.e. Gq/11. The involvement of PT-sensitive G-proteins, i.e. Gi-like and/or Go-like proteins, in the stimulation of phosphoinositide hydrolysis by ETs and SRTXs is discussed.