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Peripheral corticotropin-releasing factor (CRF) induces stimulation of gastric contractions in freely moving conscious rats: role of CRF receptor types 1 and 2

Authors


Address for Correspondence
Tsukasa Nozu, MD, PhD, FACP, FJSIM, Department of Regional Medicine and Education, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, Japan.
Tel: +81-166-68-2844; fax: +81-166-68-2846;
e-mail: tnozu@sea.plala.or.jp

Abstract

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 astressin2-B (200 μg kg−1, sc), a selective CRF receptor type 2 (CRF2) antagonist, enhanced the CRF-induced increase in MI significantly. Meanwhile urocortin 2 (15 μg kg−1, sc), a selective CRF2 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 (CRF1) agonist, mimicked the response induced by sc CRF.

Conclusions & Inferences  Peripheral CRF stimulates gastric contractions through CRF1. CRF2 activation inhibits the response induced by CRF, suggesting that CRF2 may have a modulatory action to CRF1 signaling in gastric motor activity.

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