Vasoactive intestinal peptide stimulates a cAMP-mediated Cl- current in avian salt gland cells.

VIP plays an integral role in both protein and fluid secretion in many exocrine glands. By employing the perforated patch-clamp whole-cell recording technique we investigated the effects of VIP on membrane potential and transmembrane currents in avian exocrine salt gland cells. Prior to application of VIP, salt gland cells had a resting membrane potential close to -45 mV. When challenged with VIP (1-100 nM) a sustained depolarization to ECl- was induced which was mimicked by the application of cell-permeable cAMP analogues or forskolin (1 microM). By employing the voltage-clamp recording configuration a sustained increase in current was observed with a reversal potential which approximated ECl-. Ionic substitution experiments confirmed that the current was a Cl- conductance which was inhibited by the Cl- channel blockers flufenamic acid and niflumic acid and by the inhibitory cAMP isomer, adenosine-3',5'-cyclic monophosphothioate, Rp-isomer. Based on this, and the fact that the kinetic properties of the Cl- current activated by VIP are similar to those activated by cAMP, we propose that VIP-receptor interaction results in the activation of a cAMP-dependent Cl- current.