MUSCARINIC STIMULATION OF GALLBLADDER EPITHELIUM .3. ANTAGONISM OF CAMP-MEDIATED EFFECTS

Elevation of adenosine 3',5'-cyclic monophosphate (cAMP) levels in Nec turus gallbladder (NGB) epithelium activates an apical membrane Cl- co nductance and decreases transepithelial fluid transport (J(V)). Acetyl choline (ACh), which had no effects on J(V) by itself, antagonized the electrophysiological effects of forskolin (FSK) and theophylline and the decrease in J(V) produced by FSK. By itself, ACh had no effects on basal cAMP levels but antagonized the increases in cAMP induced by FS K and theophylline. ACh had no effect on phosphodiesterase activity an d prevented both the electrophysiological response and the elevation i n cAMP by theophylline. In conclusion, the effect of ACh is mediated b y inhibition of adenylate cyclase. A pertussis toxin (PTX)-sensitive G protein may mediate inhibition of adenylate cyclase because pretreatm ent with PTX prevented the reversal of the electrophysiological effect s of FSK by ACh, and PTX catalyzed the ribosylation of cell membranes from NGB epithelium. ACh could have a physiological role in modulating the effects of secretagogues that act via elevation of cAMP levels.