[Role of "secondary transmitters" in the exocrine function of the pancreas].

In animals, exogenous secretin produces dose--related increases in pancreatic tissue levels of cyclic AMP which are closely correlated with both bicarbonate and cyclic AMP outputs in pancreatic juice. These effects can be augmented by additional administration of phosphodiesterase inhibitors such as methylxanthines. Vasoactive intestinal peptide (VIP) produces similar though less pronounced effects than secretin. Following secretion or VIP the changes in pancreatic tissue cyclic AMP concentrations precede the physiological response, i.e. enhance water and electrolyte secretion. In man, bicarbonate and cyclic AMP concentrations of pure pancreatic juice obtained by endoscopic cannulation of Vater's papilla are significantly correlated in response to both secretin and VIP. VIP however, has a lower efficacy and potency relative to secretin. There is no significant correlation between pancreatic juice cyclic GMP and bicarbonate concentrations or outputs. These observations suggest that cyclic AMP plays an important role in mediating the stimulatory effects of secretin and VIP on hydrokinetic pancreatic exocrine function. However, it still remains to be elucidated in which specific way cyclic AMP initiates the secretory process. In principle, the action of cyclic nucleotides on cell function is thought to occur from their ability to activate cyclic nucleotide--dependent protein kinases which in turn are capable of activating enzymes of protein synthesis by phosphorylation (19). With respect to pancreatic secretion, studies of this kind are currently under way.