Bombesin and nutrients stimulate release of CCK through distinct pathways in the rat

An isolated, vascularly perfused duodenojejunum model was developed in the rat to investigate the mechanisms involved in the release of cholecystokinin (CCK) by vascular bombesin (BBS) and luminal nutrients (LN). Immunoreactive peptides released into the portal vein effluent were measured with three antisera that were relatively CCK specific, gastrin specific, and cross-reactive to both CCK and gastrin, respectively. Bombesin (10(-7) M) provoked a biphasic release of CCK, consisting of a transient rise (approximately 700% above basal) followed by a sustained response (approximately 250% above basal). Gastrin accounted for less than 25% of the total immunoreactivity as measured with the nonspecific antiserum. The two phases of the CCK response were related to the dose of BBS in the range 10(-10)-10(-6) M, with a half-maximal effect at 10(-8) M BBS. Tetrodotoxin (TTX, 10(-6) M) reduced the second phase only (by 80%), whereas hexamethonium (10(-4) M) and atropine (10(-5) M) left the two phases unaltered. LN induced a prompt and well-sustained release of CCK (approximately 250% above basal) that was not affected by arterial TTX or atropine. These results demonstrate that BBS stimulated the release of CCK through both a direct pathway and an indirect, noncholinergic mechanism, while the effect of LN did not appear to involve intramural nerves.