Human urocortin II, a new CRF-related peptide, displays selective CRF(2)-mediated action on gastric transit in rats.
Human urocortin (hUcn) II is a new member of the corticotropin-releasing factor (CRF) family that selectively binds to the CRF(2) receptor. We investigated the CRF receptors involved in mediating the effects of hUcn II and human/rat CRF (h/rCRF) 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 30 min before intravenous injection of peptides or partial restraint (for 90 min). hUcn II (3 or 10 microg/kg i.v.) inhibited gastric emptying (by 45% and 55%, respectively) and did not influence distal colonic transit. The CRF(2) peptide antagonist astressin(2)-B blocked hUcn II action. h/rCRF, rat Ucn, and restraint delayed gastric emptying while accelerating distal colonic transit. The gastric response to intravenous h/rCRF and restraint was blocked by the CRF(2) antagonist but not by the CRF(1) antagonist CP-154,526, whereas the colonic response was blocked only by CP-154,526. None of the CRF antagonists influenced postprandial gut transit. These data show that intravenous h/rCRF and restraint stress-induced delayed gastric emptying involve CRF(2) whereas stimulation of distal colonic transit involves CRF(1). The distinct profile of hUcn II, only on gastric transit, is linked to its CRF(2) selectivity.
Million
Mulugeta
M
CURE: Digestive Diseases Research Center, Veterans Affairs Greater Los Angeles Healthcare System, University of California, Los Angeles 90073, USA. mmuluget@ucla.edu
Maillot
Céline
C
Saunders
Paul
P
Rivier
Jean
J
Vale
Wylie
W
Taché
Yvette
Y
D000818:Animals; D003106:Colon / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D005746:Gastric Emptying / Q000187:drug effects*; D006801:Humans; D008297:Male; D008322:Mammals; D010446:Peptide Fragments / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000503:physiopathology; D054832:Urocortins; D000099052:CRF Receptor, Type 1
C101628:CP 154526; C101531:CRF receptor type 2; D010446:Peptide Fragments; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C120841:astressin B; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone