Pancreatic glucagon and cholecystokinin synergistically inhibit sham feeding in rats.

Abstract

Pancreatic glucagon (PG) elicits satiety in normally feeding rats but fails to inhibit sham feeding in rats with open gastric cannulas. This suggests that a gastric or postgastric food stimulus is necessary for PG's satiating action. To determine whether bombesin or cholecystokinin might provide such a stimulus, sham-feeding rats received simultaneous intraperitoneal injections of 100-800 micrograms/kg of PG and doses of bombesin or cholecystokinin (CCK) that were near the threshold for inhibition of sham feeding. PG and 0.15-to 0.30-micrograms/kg CCK combinations inhibited sham feeding potently (37.6 +/- 7.0 and 62.0 +/- 9.4%, respectively). In contrast, PG and 0.25- to 0.50-microgram/kg bombesin combinations did not significantly affect sham feeding. Behavioral observations indicated that the inhibition of sham feeding by PG plus CCK did not disrupt the normal postprandial satiety sequence of behavior, PG, 400 micrograms/kg, plus 0.15 micrograms/kg of CCK did not inhibit sham drinking in 18-h water-deprived rats. PG, 400 micrograms/kg, plus 0.30 microgram/kg of CCK did inhibit sham drinking, although the effect (34.6 +/- 6.6%) was significantly less than the effect on sham feeding (75.5 +/- 9.7%) in the same rats. These data indicate that CCK is a sufficient food stimulus to permit PG to inhibit sham feeding. Furthermore, this inhibitory effect appears to result from a functional synergism of PG and CCK.