Mediation by CCKB receptors of the CCK-evoked hyperaemia in rat gastric mucosa.
1. Cholecystokinin octapeptide (CCK-8) and gastrin-17 augment gastric mucosal blood flow in the rat. The present study examined whether the gastric vasodilator effect of these peptides is mediated by CCKA or CCKB receptors. 2. Intravenous injection of CAM-1481 (1 mg kg-1), a dipeptoid antagonist of CCKA receptors, or CAM-1028, a dipeptoid CCKB receptor antagonist (1 mg kg-1), had no effect on basal gastric mucosal blood flow as determined by the clearance of hydrogen in urethane-anaesthetized rats. 3. Intravenous infusion of CCK-8 or gastrin-17 (8-200 pmol min-1) increased gastric mucosal blood flow in a dose-dependent fashion. The CCKB receptor antagonist, CAM-1028, significantly attenuated the hyperaemic response to CCK-8 and gastrin-17 whereas the CCKA receptor antagonist, CAM-1481, did not antagonize CCK-8 but caused a slight attenuation of the vasodilator response to gastrin-17. 4. The selectivity of the two antagonists was proved by the findings that CAM-1028, but not CAM-1481, inhibited gastric acid secretion evoked by CCK-8 or gastrin-17 (CCKB receptor assay) while CAM-1481, but not CAM-1028, inhibited the CCK-8-induced contraction of guinea-pig isolated gall bladder strips (CCKA receptor assay). 5. These data show that the actions of CCK-8 and gastrin-17 to increase mucosal blood flow in the rat stomach are primarily mediated by CCKB receptors.
Heinemann
A
A
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Jocic
M
M
Holzer-Petsche
U
U
Pethö
G
G
Peskar
B M
BM
Horwell
D C
DC
Holzer
P
P
D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology / Q000502:physiology*; D004151:Dipeptides / Q000494:pharmacology; D005260:Female; D005704:Gallbladder / Q000187:drug effects; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D005755:Gastrins / Q000494:pharmacology; D006168:Guinea Pigs; D006940:Hyperemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
C097931:CAM 1481; D004151:Dipeptides; D005755:Gastrins; D007211:Indoles; D011949:Receptors, Cholecystokinin; C065600:PD 135158; C013550:gastrin 17; D008536:Meglumine; D002766:Cholecystokinin