Inhibition of toad urinary bladder sodium transport by carbamylcholine: possible role of cyclic GMP

Abstract

Carbamylcholine elevates the cyclic[c]GMP content of toad urinary bladder epithelial cells without affecting cAMP content, and it inhibits Na transport. The effect on both cGMP and short-circuit current [SCC] are blocked by atropine. The time course and the concentration-response curve for the effect of carbamylcholine on cGMP and on SCC are compatible with the interpretation that elevation of epithelial cell cGMP mediates the inhibition of SCC. Elevation of epithelial cell cGMP by the Ca ionophore A23187 [2-[(3,9,11-trimethyl)8,12-pyrrolecarboxymethyl-1,7-dioxaspiro [6.6] undecyl-2-methyl]-5-methylaminobenzoxazole-4-carboxylic acid] is also associated with inhibition of SCC. Although elevation of cell cAMP usually produces an increase in SCC, there is no change in SCC in bladders exposed to isobutylmethylxanthine, which elevates cGMP as well as cAMP. Exogenous cGMP and its analogs do not alter SCC, so there is no direct evidence that the evelation of cell cGMP content causes the decrease in SCC. In view of the correlation between elevation of epithelial cell cGMP content and inhibition of Na transport that has been demonstrated, elevation of epithelial cell cGMP content apparently causes a decrease in SCC, although a direct causal relationship is not established.