Effect of a novel CCKA receptor antagonist (2-NAP) on the reduction in food intake produced by CCK in pigs

Abstract

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.