PATHWAYS MEDIATING CRF-INDUCED INHIBITION OF GASTRIC-EMPTYING IN RATS

The corticotrophin-releasing factor (CRF) is shown to be released duri ng stress suggesting that CRF has a physiological role in the mediatio n of central nervous system (CNS) response to stress, including an inh ibitory effect on gastric emptying. In the present study, we have exam ined the pathways by which intracerebroventricularly (icy) administere d CRF and central CRF activation during stress alter the gastric empty ing rate of saline (0.14 M), acid (50 mM), peptone (4.5%) and peptone after preload. The emptying rates of all these test meals were signifi cantly (p < 0.05-0.001) delayed with increasing doses of icy CRF (0.00 1, 0.003, 0.01, 0.1, 0.3 and 1 nmol/10 IJ 1), when compared with their icy saline-treated controls. The l-nmol dose of CRF inhibited the emp tying of acid, peptone and peptone after a preload by 43.8%, 64.1% and 81.1%, respectively. Twenty-minute swim stress delayed gastric emptyi ng rate of saline, acid and peptone solutions significantly (p < 0.001 ) and the CRF receptor antagonist, alpha-helical CRF (8 nmol/10 mu l, icv), applied before the swim stress, abolished the inhibitory effect of stress on the emptying rate of these solutions. Acute intragastric administration of capsaicin (2 mg/rat) and systemic capsaicin (125 mg kg(-1)) treatment facilitated the gastric emptying rate of acid, pepto ne and peptone after preload significantly, almost abolishing the inhi bitory effect of central CRF (p < 0.001). However, either capsaicin tr eatment had no effect on stress-induced inhibition of the gastric empt ying of none of the solutions, except peptone after a preload. Our fin dings demonstrate that the gastric inhibitory response induced by swim ming as a stress-producing stimulus is mediated by the endogenous rele ase of CRF. They also suggest that CRF exerts its CNS actions on the g astrointestinal tract via vago-vagal, capsaicin-sensitive pathways, pr obably involving the central cholecystokinin (CCK) mechanisms. (C) 199 7 Elsevier Science B.V. All rights reserved.