Abstract
The effect of the corticotropin-releasing factor (CRF) receptor antagonists astressin and d-Phe CRF12–41injected i.v. on CRF-induced delayed gastric emptying (GE) was investigated in conscious rats. Gastric transit was assessed by the recovery of methyl cellulose/phenol red solution 20 min after its intragastric administration. The 55% inhibition of GE induced by CRF (0.6 μg i.v.) was antagonized by 87 and 100% by i.v. astressin at 3 and 10 μg, respectively, and by 68 and 64% by i.v. d-Phe CRF12–41 at 10 and 20 μg, respectively. CRF (0.6 μg)-injected intracisternally (i.c.) induced 68% reduction of GE was not modified by i.v. astressin (10 μg) whereas i.c. astressin (3 or 10 μg) blocked by 58 and 100%, respectively, i.v. CRF inhibitory action. Abdominal surgery with cecal manipulation reduced GE to 7.1 ± 3.1 and 27.5 ± 3.3% at 30 and 180 min postsurgery, respectively, compared with 40.3 ± 4.3 and 59.5 ± 2.9% at similar times after anesthesia alone. Astressin (3 μg i.v.) completely and d-Phe CRF12–41 (20 μg i.v.) partially (60%) blocked surgery-induced gastric stasis observed at 30 or 180 min. The CRF antagonists alone (i.v. or i.c.) had no effect on basal GE. These data indicate that CRF acts in the brain and periphery to inhibit GE through receptor-mediated interaction and that peripheral CRF is involved in acute postoperative gastric ileus; astressin is a potent peripheral antagonist of CRF when injected i.v. whereas i.c. doses ≥3 μg exert dual central and peripheral blockade of CRF action on gastric transit.
Footnotes
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Send reprint requests to: Dr. Yvette Taché, Ph.D., Building 115, Room 203, West Los Angeles Veterans Administration Medical Center, 11301 Wilshire Blvd., Los Angeles, CA 90073. E-mail: ytach{at}ucla.edu
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↵1 This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, Grants DK-33061 (Y.T.), DK-26741 (J.R.), and DK-41301 (Animal Core, Y.T.).
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↵2 Present address: Centro de Estudíos Universitarios San Pablo, Veterinary School, Department of Physiology, 46113 Moncada, Valencia, Spain.
- Abbreviations:
- CRF
- corticotropin-releasing factor
- CRF-R1 and CRF-R2
- corticotrophin-releasing factor receptor subtypes 1 and 2, respectively
- CSF
- cerebrospinal fluid
- d-Phe CRF12–41
- [d-Phe12,Nle21,38,CαMeLeu37]r/h CRF12–41
- i.c.
- intracisternal
- GE
- gastric emptying
- GI
- gastrointestinal
- ACTH
- adrenocorticotropin
- r/hCRF
- rat/human CRF
- Received November 20, 1998.
- Accepted March 9, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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