Effect of a novel CCKA receptor antagonist (2-NAP) on the reduction in food intake produced by CCK in pigs.
The effect of a novel CCKA receptor antagonist 2-naphthalene sulphonyl-L-aspartyl-2-(phenethyl)amide, sodium salt (2-NAP) on the reduction of food intake induced by exogenous CCK, administered centrally or peripherally, has been examined in pigs. 2-NAP is hydrophilic and should not readily cross the blood-brain barrier. Intravenous (IV) 2-NAP (20 or 40 mg/kg) injected prior to IV CCK-8S (1 microgram/kg) abolished the inhibitory effect of CCK-8S on operant food intake in hungry pigs. Intravenous injections of 2-NAP (20 and 30 mg/kg) prior to the administration of intracerebroventricular (ICV) injection of CCK-8S (1 microgram) did not affect the inhibitory action of ICV CCK-8S on food intake. ICV injection of 2-NAP (5 mg) abolished the inhibitory effect on food intake of ICV CCK-8S (1 microgram). The results indicate that 2-NAP does not cross the blood-brain barrier readily and that central and peripheral administration of CCK-8S inhibits feeding by different mechanisms. Neither ICV nor IV injection of 2-NAP altered food intake when injected alone.
Baldwin
B A
BA
AFRC Institute of Animal Physiology and Genetics Research, Cambridge Research Station, Babraham, UK.
de la Riva
C
C
Gerskowitch
V P
VP
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005260:Female; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009282:Naphthalenesulfonates / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000145:classification; D012844:Sincalide / Q000494:pharmacology*; D014630:Vagus Nerve / Q000187:drug effects
D009282:Naphthalenesulfonates; D011949:Receptors, Cholecystokinin; C080661:N-(2-naphthalenesulfonyl)aspartyl-(2-phenethyl)amide; D001224:Aspartic Acid; D012844:Sincalide