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.
Martin
S C
SC
Department of Physiology, University of Rochester School of Medicine and Dentistry, NY 14642.
Shuttleworth
T J
TJ
D000818:Animals; D018118:Chloride Channels / Q000187:drug effects*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004372:Ducks; D004553:Electric Conductivity; D005439:Flufenamic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009544:Niflumic Acid / Q000494:pharmacology; D012491:Salt Gland / Q000166:cytology / Q000187:drug effects*; D013268:Stimulation, Chemical; D013873:Thionucleotides / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D018118:Chloride Channels; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D014660:Vasoactive Intestinal Peptide; D009544:Niflumic Acid; D005439:Flufenamic Acid; D000242:Cyclic AMP