Effect of bethanechol chloride on protein synthesis in rat pancreas

Abstract

It is well established that acetylcholine and related cholinergic drugs stimulate secretion of pancreatic digestive enzymes. However, effects of such agents on pancreatic protein synthesis have been unclear. For these experiments rats were given either saline or bethanechol chloride in doses of 0.1, 1.0, 2.0, 4.0, and 12.0 mg/kg body wt and killed after 10, 20, 40, 60, 90, 120, and 180 minutes. Pancreatic protein synthesis was measured by determiningin vitro incorporation ofl-phenylalanine-¹⁴C into whole tissue and microsomal protein fractions as well as purified amylase. Effects of bethanechol chloride on secretion were estimated by examining residual amylase content. Doses of 1.0 mg/kg resulted in 23% increases in incorporation of label into tissue proteins and 39% increases in incorporation into microsomal proteins at 20 minutes. A dose of 2.0 mg/kg resulted in 18 and 31% increases in incorporation into tissue proteins at 40 and 60 minutes as well as 34 and 14% increases in incorporation into microsomal proteins at 60 and 90 minutes. Doses of 4.0 mg/kg resulted in decreased incorporation into tissue proteins; that is, −36, −19, and −15% at 20, 40, and 60 minutes and −36, −22, and −14% decreases into microsomal proteins. A dose of 12 mg/kg was associated with −36, −38, and −28% decreases in incorporation into microsomal proteins at 60, 120, and 180 minutes. These studies show that small doses of bethanechol chloride were associated with induction of pancreatic protein synthesis and secretion. Large doses, on the other hand, were associated with decreased amino acid incorporation. These studies point out the importance of careful attention to dose and time of study.