Influence of vasoactive intestinal polypeptide on net water flux and cyclic adenosine 3',5'-monophosphate formation in the rat jejunum.

1. The effects were studied of vasoactive intestinal polypeptide (VIP), theophylline, and morphine on net water flux and cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels in the jejunum of anaesthetized rats in vivo and of VIP and morphine on adenylate cyclase activity in rat epithelial cell membranes in vitro. 2. Infusion of VIP (0.1-2 x 10(-9) mol/min/kg) dose dependently caused a reversal from net water absorption to net secretion; 2 x 10(-9) mol/min/kg enhanced the mucosal cyclic AMP content by 67%. 3. Theophylline (5 mg/ml, intraluminally) enhanced the effect of intra-arterial infusion of VIP (2 x 10(-9) mol/min/kg) as to net water secretion and increase in mucosal cyclic AMP content. 4. Pretreatment with morphine (5 mg/kg, s.c.) did not influence the effects of VIP on net water flux and on mucosal cyclic AMP content. 5. Atropine (2 mg/kg, s.c.) also failed to reduced the effect of VIP (0.4 x 10(-9) mol/min/kg) on net water flux. 6. Stimulation of adenylate cyclase activity was a function of VIP concentration over a range of 1 x 10(-10)-1 x 10(-7) M. Morphine (up to 1 x 10(-3) M) failed to influence stimulation of adenylate cyclase by VIP. 7. The finding that low doses of VIP, which already have an effect on net water flux, fail to increase cyclic AMP levels makes it likely that other mediators besides cyclic AMP are involved in the effect of VIP on net water flux. Some of the present results, however, support the assumption that VIP stimulates intestinal fluid secretion by increasing mucosal cyclic AMP levels.