Cholecystokinin secretagogue-induced gastroprotection: role of nitric oxide and blood flow.
This study was done to examine the role of CCK in gastric mucosal defense and to assess the gastroprotective roles of nitric oxide and blood flow. In rats, the CCK secretagogues oleate and soybean trypsin inhibitor augmented gastric mucosal blood flow and prevented gastric injury from luminal irritants. Type A CCK receptor blockade negated CCK secretagogue-induced gastroprotection and exacerbated gastric injury from bile and ethanol but did not block adaptive cytoprotection. CCK secretagogue-induced gastroprotection and hyperemia were negated by nonselective nitric oxide synthase (NOS) inhibition (N(G)-nitro-L-arginine methyl ester) but not by selective inducible NOS inhibition (aminoguanidine). Gastric mucosal calcium-dependent NOS activity, but not calcium-independent NOS activity, was increased following CCK and CCK secretagogues. The release of endogenous CCK plays a role in the intrinsic gastric mucosal defense system against injury from luminal irritants. The protective mechanism appears to involve increased production of nitric oxide from primarily the constitutive isoforms of NOS and a resultant increase in blood flow.
West
Sonlee D
SD
Department of Surgery, University of Texas Medical School, Houston, TX 77030, USA.
Helmer
Kenneth S
KS
Chang
Lily K
LK
Cui
Yan
Y
Greeley
George H
GH
Mercer
David W
DW
D000143:Acids; D000818:Animals; D015153:Blotting, Western; D002766:Cholecystokinin / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply*; D006146:Guanidines / Q000494:pharmacology; D006940:Hyperemia / Q000503:physiopathology; D007509:Irritants / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019301:Oleic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000502:physiology; D013276:Stomach Ulcer / Q000517:prevention & control*; D014361:Trypsin Inhibitors / Q000494:pharmacology
D000143:Acids; D004791:Enzyme Inhibitors; D006146:Guanidines; D007509:Irritants; D007527:Isoenzymes; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D014361:Trypsin Inhibitors; D019301:Oleic Acid; D009569:Nitric Oxide; D000431:Ethanol; D002766:Cholecystokinin; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester