Trypsin inhibits voltage-activated chloride conductance of toad skin

The effect of trypsin on the voltage-activated chloride conductance (G(Cl)) of toad skin was investigated. Serosal application of > 0.1 mg ml(-1) tryp sin decreased the voltage-activated G(Cl) without notable delay. The maxima l inhibition to 38% of the control values, exerted within 15 min, was in so me experiments partly or completely reversible. Chymotrypsin had much lower effect than trypsin. Mucosal application of trypsin did not have any effec t. Trypsin did neither interfere with the conductive pathway opened by supr amaximal concentrations of cAMP nor with the inhibitory effect of epinephri ne on the voltage-activated G(Cl). The effect of trypsin required influx of Ca2+ from the extracellular space. It is concluded that protease-activated receptors or trypsin-sensitive proteins in the basolateral membrane of toa d skin epithelial cells interfere with regulative steps involved in the vol tage-activation of G(Cl). This may be harmful for the segregation of epithe lial cells using this enzyme. (C) 1999 Elsevier Science Inc. All rights res erved.