APStracts 2:0174G, 1995.

Depolarization-stimulated cholecystokinin secretion is mediated by l-type calcium channels in stc-1 cells. Mangel, Allen W., Leann Scott, and Rodger A. Liddle. Departments of Medicine and Cell Biology, Duke University Medical Center, and the Durham Veterans Affairs Medical Center, Durham, NC 27710

APStracts 2:0174G, 1995.

To examine the role of calcium channels in depolarization- activated cholecystokinin (CCK) release, studies were performed in an intestinal CCK-secreting cell line, STC-1. Blockade of potassium channels with barium chloride (5 mM) increased the release of CCK by 374.6 + 46.6% of control levels. Barium-induced secretion was inhibited by the L-type calcium channel blocker, nicardipine. Nicardipine (10-9-10-5M) produced a dose-dependent inhibition in barium-stimulated secretion with an IC50 value of 0.1 uM. A second L -type calcium channel blocker, diltiazem (10-9-10-4M), also inhibited barium-induced CCK secretion with an IC50 value of 5.1 uM. By contrast, the T-type calcium channel blocker, nickel chloride (10-7 -10-3M), failed to significantly inhibit barium-induced CCK secretion. To further evaluate a role for L-type calcium channels in the secretion of CCK, the effects of the L-type calcium channel opener, Bay K 8644, were examined. Bay K 8644 (10-8-10-4M) produced a dose -dependent stimulation in CCK release with an EC50 value of 0.2 uM. Recording of single channel currents from inside-out membrane patches showed activation of calcium channels by Bay K 8644 (1 uM), with a primary channel conductance of 26.0 + 1.2 pS. It is concluded that inhibition of potassium channel activity depolarizes the plasma membrane, thereby, activating L-type, but not T-type, calcium channels. The corresponding influx of calcium serves to trigger secretion of CCK.

Received 2 August 1995; accepted in final form 15 August 1995.
APS Manuscript Number G328-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.