Enzyme secretion in mouse pancreas mediated by adenosine-3'5'-cyclic phosphate and inhibited by adenosine-3'-phosphate.

A number of hormones and neurohormones have been shown to exert their effect on their target tissues by altering the intracellular level of 3'5'-cyelic AM.1Among the processes mediated by cyclic AMP is the secretion of macro- molecules by various endocrine and exocrine glands.2-5Of particular interest to investigators studying the exocrine pancreas was the observation of Schramm and his co-workers2' 3that cyclic AMP is an intermediate in the stimulation of parotid secretion by epinephrine.In view of the close morphological and func- tional resemblance between the parotid gland and the exocrine pancreas, it seemed likely that secretion by the latter, like that by the former, was mediated by cyclic AMP.The present communication shows that secretion by mouse pancreas, which is stimulated by pancreozymin, a gastrin analogue and carbamyl choline, is indeed mediated by cyclic AMP.Furthermore, it is shown that 3'-AMIP inhibits secretion, probably by competing with cyclic AMP for its receptor site in the pancreas.Materials andMethods.-Materials:Pancreozymin was purchased from Sigma Chemical Co.Peptavlon (ICI 50,123) a synthetic gastrin-like pentapeptide with the following structure: t-butyloxycarbonyl-3-Ala.Try.Met.Asp.Phe.NH2,6 was the generous gift of Drs.J. D. Fitzgerald and J. A. Waycott of Imperial Chemical Industries, Ltd. 35-cyclic AMP was obtained from Sigma Chemical Co. or P-L Biochemicals.N6-2'-O dibutyryl cyclic AMP was purchased from Boehringer und Soehne.N6-monobutyryl cyclic AMP was prepared from dibutyryl cyclic AMP by the method of Falbriard et al.7 3'-AMP was the product of Schwartz BioResearch, P-L Biochemicals, or Waldhof; 5'-AMP was obtained from Schwartz BioResearch; Inderal (propanolol) hydrochloride was a gift from I.C.I.; epinephrine bitartrate and norepinephrine