THE TROPHIC RESPONSE OF RAT PANCREAS TO SULFATED CHOLECYSTOKININ-8 ISDOSE-DEPENDENT AND TIME-DEPENDENT AND NOT AFFECTED BY VAGOTOMY OR ATROPINE

Cholecystokinin (CCK) stimulates pancreatic enzyme secretion and growt h. This study establishes the dose/ plasma concentration - and time - response relationships for the trophic effect of CCK on the rat pancre as and evaluates the importance of vagal innervation and muscarinic re ceptors for the trophic effect. Rats received sulfated CCK-8 (CCK-8s) by continuous subcutaneous infusion. Different doses and different tim es of treatment were tested. The trophic effect was determined as wet weight and DNA content of the pancreas. The pancreatic weight and DNA content were found to depend not only on the plasma concentration of C CK-ss but also on the duration of treatment. The EC(50) value was 40 p moles CCK-8s per liter. This value should be compared with plasma CCK- 8s concentrations of 2-4 pmol/l in intact fed rats. Maximum trophic ef fect was observed after 7-14 days of infusion. We conclude that althou gh physiologically relevant concentrations of CCK-8s may be important for the maintenance of the pancreas they do not induce growth. In anot her experiment atropinized, vagally denervated and intact rats were tr eated with a maximally effective dose of CCK for four days. The trophi c effect of CCK-8s was unaffected by vagotomy or atropinization.