Central injection of a new corticotropin-releasing factor (CRF) antagonist, astressin, blocks CRF- and stress-related alterations of gastric and colonic motor function

The influence of central injection of a new corticotropin releasing factor (CRF) antagonist, astressin, {cyclo(30-33)[D-Phe(12),Nle(21,38),Glu(30),Lys(33)]r/hCRF(12-41)}, on exogenous and endogenous CRF-induced gastric ileus and stimulation of bowel discharges was investigated in conscious rats. Intracisternal (ic) CRF (0.6 mu g) reduced gastric emptying of a noncaloric solution to 17.1 +/- 4.9% compared with 50.1 +/- 4.6% in control group injected ic with vehicle. Astressin (1, 3 and 10 mu g, ic) dose dependently prevented ic CRF-induced delayed gastric emptying by 33, 100 and 100%, respectively, and had no effect on basal gastric emptying. Abdominal surgery with cecal manipulation (1 min) reduced gastric emptying to 19.8 +/- 5.5% 3 hr postsurgery compared with 59.9 +/- 5.2% after anesthesia alone plus ic vehicle. Astressin (1, 3 and 10 mu g, ic) prevented postoperative gastric ileus by 56, 93 and 92%, respectively. Intracerebroventricular CRF (0.6 mu g) and water-avoidance stress stimulated pellet output (number/60 min) to 5 +/- 1 and 11 +/- 2, respectively, compared with no fecal pellet output after icv vehicle and no exposure to stress. Astressin (3 and 10 mu g, icv) blocked exogenous CRF action by 47 and 63%, respectively, and colonic response to stress by 0 and 54%, respectively. These data indicate that astressin injected into the CSF at low doses (1-10 mu g) has an antagonistic action against CRF and stress-related alterations of gastrointestinal motor function, without an intrinsic effect in these in vivo systems. Astressin may be a useful tool to explore functional CRF-dependent physiological pathways in specific brain nuclei.