Effects of inhibitors of cyclic nucleotide phosphodiesterase on the actions of vasoactive intestinal peptide and secretin on pancreatic acini

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Abstract
Theophylline, 3-isobutyl-1-methylxanthine (IBMX), and Ro 20-1724 [racemic-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone] each augmented the increase in cAMP and the stimulation of amylase secretion caused by vasoactive intestinal peptide (VIP) or secretin [in guinea pig]. With IBMX the dose-response curve for the stimulation of amylase secretion caused by VIP or secretin spanned a range of lower concentrations than did that obtained with Ro 20-1724, which in turn spanned a range of lower concentrations than did that obtained with theophylline. The configuration of the dose-response curve for the action of VIP on cAMP differed with each phosphodiesterase inhibitor tested. With Ro 20-1724 the dose-response curve was monophasic, while with the 2 methylxanthines the dose-response curve was biphasic. With theophylline the magnitude of the 2nd component of the dose-response curve was larger than the 1st; with IBMX the magnitude of the 1st component was larger than the 2nd. The configuration of the dose-response curve for the action of secretin on cAMP differed with each phosphodiesterase inhibitor tested. With theophylline thedose-response curve was monophasic, while with Ro 20-1724 and IBMX the dose-response curve was biphasic. With Ro 20-1724 the magnitude of the 2nd component of the dose-respone curve was larger than the 1st; with IBMX the magnitude of the 1st component was larger than the 2nd. cAMP may be compartmentalized in pancreatic acinar cells and the different compartments of cAMP are apparently affected differently by various inhibitors of cyclic nucleotide phosphodiesterase. The different compartments of cAMP may be acted on by phosphodiesterases with different sensitivities to various inhibitors.