Regulation of cholecystokinin secretion in stc-1 cells by nitric oxide. Mangel, Allen W., Leann Scott, Veronica Prpic, and Rodger A. Liddle. DEPARTMENT OF MEDICINE, DUKE UNIVERSITY MEDICAL CENTER, DURHAM, NC 27710; GLAXO WELLCOME INC., RESEARCH TRIANGLE PARK, NC 27709; AND THE DURHAM VETERANS AFFAIRS MEDICAL CENTER, DURHAM, NC 27710
APStracts 3:0069G, 1996.
In the present study, we evaluated the effects of agents anticipated to change NO levels on the secretion of cholecystokinin (CCK) from STC-1. Following 15 minute treatment with the NO generating agent, sodium nitroprusside (SNP; 10 uM), a 24% inhibition in basal CCK release and an increase in cellular cGMP levels were noted. By contrast, SNP (10 uM) had no effect on CCK release stimulated by L -phenylalanine (20 mM). Inhibition of NO synthase (NOS) with L-NAME produced dose-dependent stimulation in CCK release. L-NAME (100-400 uM) also inhibited ATP-sensitive potassium (KATP) channels in cell -attached patches. Pretreatment of cells with disopyramide (200 uM), a KATP channel blocker, blocked L-NAME stimulation of CCK release. Following inhibition in potassium channel activity by L-NAME, addition of the nonhydrolyzable cGMP analogue, 8-Br-cGMP (1-2 mM), reactivated potassium channels. NO generating agents had no effect on channel activity in inside-out membrane patches. It is concluded that NO may serve as an important regulator of basal CCK release.

Received 6 October 1996; accepted in final form 19 March 1996.
APS Manuscript Number G432-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 April 96