The present study was undertaken in order to delineate the contribution of enteric bombesin (BBS)-containing nerves in the food-induced release of intestinal cholecystokinin (CCK). For this purpose, the isolated vascularly perfused rat duodenojejunum model was used and the new compound [Leu14-psi(CH2NH)-Leu13]BBS was infused intraarterially at a concentration of 10(-6) M to block the BBS receptors. Vascular infusion of BBS alone (10(-8) M or 10(-9) M) provoked a dose-dependent release of CCK-like immunoreactivity (CCK-LI). The secretion pattern of CCK was biphasic and consisted of a transient peak (300-400% above basal) followed by a sustained response (200-300% above basal). Vascular coinfusion of the BBS analogue with BBS 10(-9) M completely abolished both phases of CCK release while only the second phase of CCK secretion was profoundly reduced upon coadministration of BBS 10(-8) M with the BBS receptor antagonist. Luminal administration of mixed nutrients induced a prompt and well-sustained release of CCK-LI which was unaffected upon arterial infusion of the BBS analogue. These data suggest that the intestinal supply in BBS-producing nerves is not involved in the food-induced release of intestinal CCK in the rat.