Variable effect of lithium on canine pancreatic polypeptide and gastrin release by a meal or bombesin

Lithium is a cation which has central nervous system effects and is able to interfere with both the release and action of polypeptide hormones. We examined its effect on basal and stimulated plasma gastrin and pancreatic polypeptide (PP) levels in 4 dogs with chronic gastric fistulas. Gastrin and PP release were stimulated by a meal or bombesin nonapeptide infusion (1.2 microgram kg-1h-1). The studies were repeated 24h and 14 days after lithium administration (600 mg/12 h) orally. Basal plasma lithium values were undetectable and rose to 0.9 /+- 0.2 mmol l-1 in the acute and 1.0 +/- 0.2 mmol l-1 in the chronically treated animals. The dogs did not have any discernible side effects. Basal plasma gastrin was 14 +/- 4 fmol ml -1 and was not significantly altered by either 1 or 14 days Li+( p greater than 0.05). Gastrin release stimulated by either a meal or bombesin was not significantly decreased by acute or chronic Li+ administration . Acute lithium administration produced a slight but significant increase in meal-stimulated gastrin (p less than 0.01). Neither acute nor chronic lithium administration altered bombesin stimulated gastric acid secretin (p greater than 0.05). Basal PP levels were 24 +/- 7 fmol ml-1 and not significantly altered by 1 or 14 days Li+ administration. Both acute and chronic Li+ inhibited PP release by bombesin in the first 30-min period of the study (p less than 0.01). 14 days Li+ significantly inhibited both first and second hour PP responses to a meal (p less than 0.01). The mechanism of the cationic modification of the release of pancreatic polypeptide requires further elucidation.