Peripheral corticotropin-releasing factor (CRF) induces stimulation of colonic contractions and visceral hyperalgesia in rats; role of CRF receptor type 1 and 2

Purpose. To determine the role of peripheral CRF receptor subtype 1 and 2 (CRF1 and 2) signaling in mediating colonic contractions and visceral sensation in rats. Methods. Colonic contractions were measured by the perfused manometry. Visceromotor response (VMR) was assessed by electrophysiologically measuring the contractions of abdominal muscle in response to colorectal distensions (CRD, 60 mmHg for 10 min twice with 30 min rest). All drugs were administered through intraperitoneal route. In VMR study, the drugs were injected at the end of the first CRD. Results. CRF increased colonic contractions. Pretreatment with astressin, a non-selective CRF antagonist, blocked this CRF-induced stimulation but astressin 2B (Ast2B), a selective CRF2 antagonist, enhanced it. Cortagine, a selective CRF1 agonist, increased but urocortin 2 (Ucn2), a selective CRF2 agonist, did not alter the contractions. VMR during the second CRD was significantly higher than that of the first. Astressin blocked but Ast2B or CRF did not affect this CRD-induced sensitization. Meanwhile, Ast2B together with CRF significantly enhanced the sensitization. Ucn2 blocked but cortagine enhanced the sensitization. Conclusions. Peripheral CRF stimulates colonic contractions and induces visceral sensitization through CRF1. CRF2 activation inhibits these responses, suggesting that CRF2 may have a modulatory and counter regulatory action to CRF1 signaling in colonic motor and sensory function.