Previous studies have demonstrated mostly inhibitory effects of elevated plasma glucose levels on gastric exo- and endocrine as well as motor functions. Because increased plasma glucose levels reduce vagal activity via the central nervous system, it remains unclear if glucose exerts a direct effect on gastric functions. Therefore, our study was designed to determine the effect of acute changes in glucose concentrations on the release of gastrin and bombesin-like immunoreactivity (BLI) from the isolated perfused rat stomach. Acute elevations of perfusate glucose from 100 to 200 mg/dl or from 100 to 300 mg/dl augmented BLI secretion significantly without affecting gastrin release. During an acute decrease from 200 to 30 mg/dl, the secretion of both peptides remained unchanged. When acetylcholine was administered to stimulate BLI and gastrin secretion, the elevation of perfusate glucose to 200 mg/dl and the decrease to 30 mg/dl attenuated BLI secretion, whereas gastrin secretion remained unchanged compared with the control experiments at 100 mg/dl glucose. On the other hand, the perfusion of vasoactive intestinal peptide (VIP) and Leu-enkephalin had no effect on BLI and gastrin secretion during 100 mg/dl glucose perfusion, but both peptides elicited a significant stimulatory effect on BLI secretion during a perfusate glucose concentration of 200 mg/dl without affecting gastrin secretion. In conclusion, our study demonstrates first that an acute increase of glucose augments basal BLI secretion. Second, cholinergically induced BLI secretion is attenuated by hypo- and hyperglycemia. Third, hyperglycemia augments BLI secretion in response to the neuropeptides VIP and Leu-enkephalin. Fourth, basal and stimulated gastrin secretion remains unchanged during acute alterations of perfusate glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS)