REGULATION OF CHOLECYSTOKININ SECRETION IN STC-1 CELLS BY NITRIC-OXIDE

In the present study, we evaluated the effects of agents anticipated t o change NO levels on the secretion of cholecystokinin (CCK) from STC- 1 cells. After a 15-min treatment with the nitric oxide (NO)-generatin g agent sodium nitroprusside (SNP; 10 mu M), a 24% inhibition in basal CCK release and an increase in cellular guanosine 3',5'-cyclic monoph osphate (cGMP) levels were noted. By contrast, SNP (10 mu M) had no ef fect on CCK release stimulated by L-phenylalanine (20 mM). Inhibition of NO synthase (NOS) with N-G-nitro-L-arginine methyl ester (L-NAME) p roduced dose-dependent stimulation in CCK release. L-NAME (100-400 mu M) also inhibited ATP-sensitive potassium (K-ATP) channels in cell-att ached patches. Pretreatment of cells with disopyramide (200 mu M), a K -ATP channel blocker, blocked L-NAME stimulation of CCK release. After inhibition of potassium channel activity by L-NAME, addition of the n onhydrolyzable cGMP analogue 8-bromo-cGMP (1-2 mM) reactivated potassi um 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.