CONTRASTING EFFECTS OF PACAP AND CARBACHOL ON [CA-2-OK-1 CELLS(]I ANDINOSITOL PHOSPHATES IN HUMAN NEUROBLASTOMA NB)

The effects of PACAPs on [Ca2+]i were compared to those of carbachol i n human neuroblastoma NB-OK-1 cells. PACAP(1-27) and PACAP(1-38) incre ased [Ca2+]i in a biphasic manner: a transient rise and a secondary pl ateau. The transient phase reflected the mobilization of [Ca2+]i pool( s) via the inositol phosphate pathway. The modest sustained plateau re quired extracellular Ca2+. Carbachol also increased [Ca2+]i in a bipha sic manner, but it mobilized intracellular Ca2+ pool(s) with a higher efficacy than PACAPs, then greatly increased Ca2+ entry, this being ac companied by a more marked and prolonged elevation of IP3 and IP4 than with PACAPs. It is likely that cAMP-mediated phosphorylations due to PACAPs facilitated desensitization at the PACAP receptor-phospholipase C level, so that there was less Ca2+ handling through PACAP receptors than with muscarinic M1 receptors.