Regulation of cholecystokinin secretion in STC-1 cells by nitric oxide.
In the present study we evaluated the effects of agents anticipated to change NO levels on the secretion of cholecystokinin (CCK) from STC-1 cells. After a 15-min treatment with the nitric oxide (NO) generating agent sodium nitroprusside (SNP; 10 microM), a 24% inhibition in basal CCK release and an increase in cellular guanosine 3',5'-cyclic monophosphate (cGMP) levels were noted. By contrast, SNP (10 microM) had no effect on CCK release stimulated by L-phenylalanine (20 mM). Inhibition of NO synthase (NOS) with NG-nitro-L-arginine methyl ester (L-NAME) produced dose-dependent stimulation in CCK release. L-NAME (100-400 microM) also inhibited ATP-sensitive potassium (KATP) channels in cell-attached patches. Pretreatment of cells with disopyramide (200 microM), a KATP channel blocker, blocked L-NAME stimulation of CCK release. After inhibition of potassium channel activity by L-NAME, addition of the nonhydrolyzable cGMP analogue 8-bromo-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.
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
A W
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Mangel
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L
Scott
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Prpic
R A
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Liddle
D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D004206:Disopyramide / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D009599:Nitroprusside; D009569:Nitric Oxide; D002766:Cholecystokinin; D004110:Diltiazem; D004206:Disopyramide; D011188:Potassium; D002118:Calcium