BACKGROUND: Peripheral corticotrophin-releasing factor (CRF) plays an important role in stress-induced alterations of gastrointestinal motility. CRF injected peripherally inhibits gastric emptying, but its effect on gastric contractions has not been clarified in freely moving conscious rats. METHODS: Intraluminal gastric pressure waves were measured in freely moving conscious non-fasted rats using the perfused manometric method. We assessed the area under the manometric trace as the motor index (MI), and compared this result with those obtained 1 h before and after drug administration. KEY RESULTS: Subcutaneous injection (sc) of CRF (15 μg kg(-1)) increased the MI significantly. Pretreatment with intravenous astressin (100 μg kg(-1)), a non-selective CRF antagonist, blocked the sc CRF (15 μg kg(-1))-induced response, but astressin(2)-B (200 μg kg(-1), sc), a selective CRF receptor type 2 (CRF(2)) antagonist, enhanced the CRF-induced increase in MI significantly. Meanwhile urocortin 2 (15 μg kg(-1), sc), a selective CRF(2) agonist, did not alter the basal MI, but it inhibited the sc CRF (15 μg kg(-1))-induced stimulation of gastric contractions. The intraperitoneal injection of cortagine (30 μg kg(-1)), a selective CRF receptor type 1 (CRF(1)) agonist, mimicked the response induced by sc CRF. CONCLUSIONS & INFERENCES: Peripheral CRF stimulates gastric contractions through CRF(1). CRF(2) activation inhibits the response induced by CRF, suggesting that CRF(2) may have a modulatory action to CRF(1) signaling in gastric motor activity.
BACKGROUND: Peripheral corticotrophin-releasing factor (CRF) plays an important role in stress-induced alterations of gastrointestinal motility. CRF injected peripherally inhibits gastric emptying, but its effect on gastric contractions has not been clarified in freely moving conscious rats. METHODS: Intraluminal gastric pressure waves were measured in freely moving conscious non-fasted rats using the perfused manometric method. We assessed the area under the manometric trace as the motor index (MI), and compared this result with those obtained 1 h before and after drug administration. KEY RESULTS: Subcutaneous injection (sc) of CRF (15 μg kg(-1)) increased the MI significantly. Pretreatment with intravenous astressin (100 μg kg(-1)), a non-selective CRF antagonist, blocked the sc CRF (15 μg kg(-1))-induced response, but astressin(2)-B (200 μg kg(-1), sc), a selective CRF receptor type 2 (CRF(2)) antagonist, enhanced the CRF-induced increase in MI significantly. Meanwhile urocortin 2 (15 μg kg(-1), sc), a selective CRF(2) agonist, did not alter the basal MI, but it inhibited the sc CRF (15 μg kg(-1))-induced stimulation of gastric contractions. The intraperitoneal injection of cortagine (30 μg kg(-1)), a selective CRF receptor type 1 (CRF(1)) agonist, mimicked the response induced by sc CRF. CONCLUSIONS & INFERENCES: Peripheral CRF stimulates gastric contractions through CRF(1). CRF(2) activation inhibits the response induced by CRF, suggesting that CRF(2) may have a modulatory action to CRF(1) signaling in gastric motor activity.
Authors: Ann T Hanna-Mitchell; Amanda Wolf-Johnston; James R Roppolo; Tony C A Buffington; Lori A Birder Journal: J Endocrinol Date: 2014-05-14 Impact factor: 4.286