ACTIVATION OF THE VASOPRESSIN-SENSITIVE WATER PERMEABILITY PATHWAY INTHE TOAD BLADDER BY N-ETHYL MALEIMIDE

Vasopressin stimulates transepithelial water flow in the toad urinary bladder. We report here that N-ethyl maleimide (NEM) (0.1 mM) produces a similar increase in osmotic water flow when applied to the mucosal surface of the tissue. NEM-induced water flow is sensitive to inhibito rs of hormone-induced water flow, including serosal acidification, or exposure to quinidine or cytoskeleton-disruptive drugs. NEM-induced wa ter flow is additive with that induced by a submaximal, but not a maxi mal, dose of vasopressin. The response to mucosal NEM is not reversed on removal of the reagent, but established NEM-induced water flow can be inhibited by serosal acidification or quinidine. Like vasopressin, mucosal NEM induces the appearance of fusion profiles and intramembran ous particle aggregates (putative water channels) in the apical plasma membrane of the granular cells, and the incidence of particle aggrega tes correlates with water flow. NEM does not cause an increase in intr acellular cAMP. Our data suggest that NEM stimulates transepithelial w ater flow by irreversibly activating cellular mechanisms normally trig gered by Vasopressin, hence causing the insertion of water channels.