The trophic response of rat pancreas to sulfated cholecystokinin-8 is dose- and time-dependent and not affected by vagotomy or atropine.

Cholecystokinin (CCK) stimulates pancreatic enzyme secretion and growth. This study establishes the dose/plasma concentration--and time--response relationships for the trophic effect of CCK on the rat pancreas and evaluates the importance of vagal innervation and muscarinic receptors for the trophic effect. Rats received sulfated CCK-8 (CCK-8s) by continuous subcutaneous infusion. Different doses and different times 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 CCK-8s but also on the duration of treatment. The EC50 value was 40 pmoles 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 effect was observed after 7-14 days of infusion. We conclude that although physiologically relevant concentrations of CCK-8s may be important for the maintenance of the pancreas they do not induce growth. In another experiment atropinized, vagally denervated and intact rats were treated with a maximally effective dose of CCK for four days. The trophic effect of CCK-8s was unaffected by vagotomy or atropinization.