VIP and forskolin enhance carbachol-induced K+ efflux from rat salivary gland fragments by a Ca2(+)-sensitive mechanism.
The effect of vasoactive intestinal peptide (VIP) and forskolin on carbachol-induced K+ release from superfused rat submandibular and parotid gland fragments was examined using a K(+)-sensitive electrode. Carbachol (0.1, 1, and 10 microM) superfused over the glandular fragments for 15 min caused a concentration-dependent, transient elevation of K+ efflux, with a peak value after approximately 5 min. The carbachol-induced release of K+ could be divided into two distinct components, one transient peak lasting 5-8 min independent of extracellular Ca2+ and a second component of K+ release dependent on Ca2+ in the perfusion medium. VIP (1 microM) lacked effect on K+ efflux on its own but increased the carbachol (1 microM)-evoked K+ release. The VIP effects on K+ efflux were mimicked by forskolin (10 microM). Omission of Ca2+ from the medium totally abolished the augmenting effect of VIP and forskolin on carbachol-evoked K+ efflux. The Ca2+ ionophore A23187 (1 or 10 microM) induced a prolonged low-rate efflux of K+, which was dependent on Ca2+ in the medium. This effect of A23187 on K+ secretion was potentiated by forskolin (10 microM). The Na(+)-K(+)-ATPase blocker ouabain did not affect K+ release on its own, a lack of effect which remained following pretreatment with forskolin. It is concluded that VIP, by increasing the intracellular levels of cAMP in the glandular cell, potentiates carbachol-evoked Ca2(+)-dependent K+ efflux. These results may help to explain the synergistic effects of the coexisting transmitters VIP and acetylcholine.
Larsson
O
O
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Detsch
T
T
Fredholm
B B
BB
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D004357:Drug Synergism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D000001:Calcimycin; D010042:Ouabain; D002217:Carbachol; D011188:Potassium; D002118:Calcium