We examined the effect of porcine gastrin-releasing peptide (GRP-27) and other analogous neuropeptides on cholecystokinin (CCK) secretion from the isolated perfused rat duodenum. GRP-27 stimulated CCK secretion in a monophasic pattern and in a dose-dependent manner ranging from 10(-9) M to 10(-6) M, and 10(-7) M of GRP-27 led to an increment of 442 +/- 120.8 fmol/3 min. The stimulatory effect of GRP-27 on CCK was not inhibited by 10(-5) M of atropine. 10(-7) M of neuromedin C and B, analogs of GRP, stimulated CCK secretion to increments of 382 +/- 64.1 and 289 +/- 47.2 fmol/3 min, respectively. Carbachol (10(-9) to 10(-6) M), VIP (10(-9)M), secretin (10(-9)M) and glucose (11 mM) did not stimulate CCK secretion, and the addition of atropine (10(-5)M) to them led to no significant changes. These results suggest that GRP may directly stimulate CCK secretion from the duodenum and work as a non-cholinergic, peptidergic neurotransmitter.