Arachidonic acid release in cell tines transfected with muscarinic receptors: A simple functional assay to determine response of agonists

Muscarinic agonists stimulated arachidonic acid release from 10- to 32-fold in Chinese hamster ovary (CHO) cells transfected with muscarinic M-1, M-3 and M-5 receptor subtypes. Muscarinic agonists liberated arachidonic acid from the cAMP-coupled M-2 and M-4 cells only in the presence of ATP. Partial agonists were less efficacious at liberating arachidonic acid than full agonists. The ability of muscarinic agonists to liberate ara chidonic acid and stimulate phosphoinositide hydrolysis in the same CHO M-1, M-3 and M-5 cells was well correlated; however, partial agonists were more efficacious at stimulating phosphoinositide hydrolysis than arachidonic acid release. The efficacy and potency of 13 muscarinic agonists to liberate arachidonic acid was characterised. Influx of external calcium was required for arachidonic acid release even after initiation of agonist-induced release. It is concluded that arachidonic acid release is a simple assay suitable for evaluation of muscarinic agonists, antagonists and the flux of external calcium into cells. CELL SIGNAL 11;6:405-413, 1999. (C) 1999 Elsevier Science Inc.