AN INVESTIGATION INTO THE RELATIVE MERITS OF PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP-27) AND VASOACTIVE INTESTINAL POLYPEPTIDE AS VAGAL NEUROTRANSMITTERS IN EXOCRINE PANCREAS OF RATS

Pancreatic exocrine secretions were collected over 15 min periods and analysed in terms of weight of juice, total HCO3- and total protein in anaesthetized and pithed rats. Pituitary adenylate cyclase-activating polypeptide (PACAP) (I.V.) evoked a serous HCO3- secretion which cont ained relatively little protein, together with a marked vasodepressor action. The latter was still maximal at lower doses of PACAP, which ev oked diminished pancreatic secretions. The effects of PACAP were simil ar to those evoked by the same dose of VIP and by cervical vagal stimu lation, while secretin evoked a much larger secretion of fluid and HCO 3-. The time courses of the PACAP-evoked secretions were significantly delayed compared with those of VIP. In the pithed rat, PACAP caused t he same lever of pancreatic secretions as in the anaesthetized rat, th ough this was now accompanied by a substantial presser response which was blocked by phentolamine or prazosin, indicating that it was alpha( 1)-adrenoceptor mediated. VIP caused a depressor response in the pithe d rat, as well as the same level of pancreatic secretions as in the an aesthetized rat. The putative VIP antagonist [Lys(1),Pro(25),Arg(3,4), Tyr(6)]-VIP (abbreviated as VIPi) caused a selective and significant r eduction in the HCO,- secretion evoked by VIP and blocked the vasodepr essor response caused by VIP. By contrast, VIPi did not antagonize eit her the secretory or vasodepressor actions of PACAP. Unilateral electr ical stimulation of the cervical vagus nerve evoked significant increa ses in the weight of juice, total protein and total HCO3- secreted. Wh en preceded by injection of VIPi, vagally evoked secretions were uncha nged in terms of weight of juice and total protein but had a significa ntly reduced HCO3- content. These results are consistent with the rele ase of VIP, though not PACAP, as a vagal neurotransmitter in the exocr ine pancreas.