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Articles in PresS, published online ahead of print September 21, 2001
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00283.2001
Submitted on June 28, 2001
Accepted on September 12, 2001
1 Medicine, Division of Digestive Disease, UCLA, Los Angeles, CA, USA
2 Clayton Found. for Peptide Biology, Salk Institute, La Jolla, CA, USA
* To whom correspondence should be addressed. E-mail: ytache{at}ucla.edu.
Human urocortin (hUcn) II is a new member of the corticotropin-releasing factor (CRF) family that selectively binds to CRF2 receptor. We investigated the CRF receptors involved in hUcn II and human/rat (h/r) CRF on gut transit. Gastric emptying, 4 h after a solid meal, and distal colonic transit (bead expulsion time) were monitored simultaneously in conscious rats. CRF antagonists were given subcutaneously (sc) 30 min before intravenous (iv) injection of peptides or partial restraint (90 min). Human Ucn II (3 or 10 µg/kg, iv) inhibited gastric emptying by 45% and 55% respectively, while not influencing distal colonic transit. The CRF2 peptide antagonist, Astressin2-B blocked hUcn II action. Human/ratCRF, rUcn and restraint delayed gastric emptying while accelerating distal colonic transit. The gastric response to iv h/rCRF and restraint was blocked by the CRF2 antagonist but not by the CRF1 antagonist, CP-154,526, while the colonic response was blocked only by CP-154,526. None of the CRF antagonists influenced post-prandial gut transit. These data show that iv h/rCRF and restraint stress-induced delayed gastric emptying involve CRF2 and stimulation of distal colonic transit involve CRF1. The distinct profile of hUcn II, only on gastric transit, is linked to its CRF2 selectivity.
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