Proposed mechanism of cholinergic action in smooth muscle

An increased turnover of phosphatidate and phosphatidyl inositol has been found in many tissues where hormones or neurotransmitters are postulated to raise Ca 2+ influx 1 , for example in smooth muscle 2–4 . However, the relationship between changes in phospholipid metabolism and changes in Ca 2+ permeability was unknown. Following recent reports on the interactions of Ca 2+ with phosphatidic acid in membranes and artificial systems, we investigated the hypothesis that phosphatidate accumulation mediates the action of cholinergic and other stimuli on Ca 2+ influx. We report here that synthesis and accumulation of phosphatidate was accelerated in smooth muscle cells stimulated by carbamylcholine with a similar time course to that of contraction. This alteration in phosphatidate metabolism does not seem to result from an increase in intracellular Ca 2+ or depolarisation of the cell membrane. Furthermore, submicromolar concentrations of phosphatidate rapidly produce contractions of isolated smooth muscle cells. These results support the contention that cholinergic-induced changes in membrane Ca 2+ permeability in smooth muscle could be mediated by phosphatidate accumulation.