Central Injection of a New Corticotropin-Releasing Factor (CRF) Antagonist, Astressin, Blocks CRF- and Stress-Related Alterations of Gastric and Colonic Motor Function

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Vol. 280, Issue 2, 754-760, 1997

Central Injection of a New Corticotropin-Releasing Factor (CRF) Antagonist, Astressin, Blocks CRF- and Stress-Related Alterations of Gastric and Colonic Motor Function¹

Vicente Martínez, Jean Rivier², Lixin Wang and Yvette Taché

CURE: Digestive Diseases Research Center, West Los Angeles VA Medical Center, Department of Medicine and Brain Research Institute, UCLA School of Medicine, Los Angeles, California

The influence of central injection of a new corticotropin releasing factor (CRF) antagonist, astressin, {cyclo(30-33)[D-Phe¹²,Nle^21,38,Glu³⁰,Lys³³]r/hCRF_12-41)}, on exogenous and endogenous CRF-inducedgastric ileus and stimulation of bowel discharges was investigatedin conscious rats. Intracisternal (ic) CRF (0.6 µg) reduced gastricemptying of a noncaloric solution to 17.1 ± 4.9% compared with50.1 ± 4.6% in control group injected ic with vehicle. Astressin(1, 3 and 10 µg, ic) dose dependently prevented ic CRF-induceddelayed gastric emptying by 33, 100 and 100%, respectively, andhad no effect on basal gastric emptying. Abdominal surgery withcecal manipulation (1 min) reduced gastric emptying to 19.8 ±5.5% 3 hr postsurgery compared with 59.9 ± 5.2% after anesthesiaalone plus ic vehicle. Astressin (1, 3 and 10 µg, ic) preventedpostoperative gastric ileus by 56, 93 and 92%, respectively. IntracerebroventricularCRF (0.6 µg) and water-avoidance stress stimulated pellet output(number/60 min) to 5 ± 1 and 11 ± 2, respectively, compared withno fecal pellet output after icv vehicle and no exposure to stress.Astressin (3 and 10 µg, icv) blocked exogenous CRF action by 47and 63%, respectively, and colonic response to stress by 0 and54%, respectively. These data indicate that astressin injectedinto the CSF at low doses (1-10 µg) has an antagonistic actionagainst CRF and stress-related alterations of gastrointestinalmotor function, without an intrinsic effect in these in vivo systems.Astressin may be a useful tool to explore functional CRF-dependentphysiological pathways in specific brain nuclei.

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				K. Kojima, Y. Naruse, N. Iijima, N. Wakabayashi, S. Mitsufuji, Y. Ibata, and M. Tanaka HPA-axis responses during experimental colitis in the rat Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2002; 282(5): R1348 - R1355. [Abstract] [Full Text] [PDF]

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				N. Kihara, M. Fujimura, I. Yamamoto, E. Itoh, A. Inui, and M. Fujimiya Effects of central and peripheral urocortin on fed and fasted gastroduodenal motor activity in conscious rats Am J Physiol Gastrointest Liver Physiol, March 1, 2001; 280(3): G406 - G419. [Abstract] [Full Text] [PDF]

				E A MAYER The neurobiology of stress and gastrointestinal disease Gut, December 1, 2000; 47(6): 861 - 869. [Full Text] [PDF]

				J Jones, J Boorman, P Cann, A Forbes, J Gomborone, K Heaton, P Hungin, D Kumar, G Libby, R Spiller, et al. British Society of Gastroenterology guidelines for the management of the irritable bowel syndrome Gut, November 1, 2000; 47(90002): ii1 - 19. [Full Text] [PDF]

				A. Inui Cancer Anorexia-Cachexia Syndrome: Are Neuropeptides the Key? Cancer Res., September 1, 1999; 59(18): 4493 - 4501. [Abstract] [Full Text] [PDF]

				V. Martínez, J. Rivier, and Y. Taché Peripheral Injection of a New Corticotropin-Releasing Factor (CRF) Antagonist, Astressin, Blocks Peripheral CRF- and Abdominal Surgery-Induced Delayed Gastric Emptying in Rats J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 629 - 634. [Abstract] [Full Text]

				T. Nozu, V. Martinez, J. Rivier, and Y. Tache Peripheral urocortin delays gastric emptying: role of CRF receptor 2 Am J Physiol Gastrointest Liver Physiol, April 1, 1999; 276(4): G867 - G874. [Abstract] [Full Text] [PDF]

				M. Million, Y. Tache, and P. Anton Susceptibility of Lewis and Fischer rats to stress-induced worsening of TNB-colitis: protective role of brain CRF Am J Physiol Gastrointest Liver Physiol, April 1, 1999; 276(4): G1027 - G1036. [Abstract] [Full Text] [PDF]

				L. K. Singh, W. Boucher, X. Pang, R. Letourneau, D. Seretakis, M. Green, and T. C. Theoharides Potent Mast Cell Degranulation and Vascular Permeability Triggered by Urocortin Through Activation of Corticotropin-Releasing Hormone Receptors J. Pharmacol. Exp. Ther., March 1, 1999; 288(3): 1349 - 1356. [Abstract] [Full Text]

				F.-C. Chang and M. R. Opp Blockade of corticotropin-releasing hormone receptors reduces spontaneous waking in the rat Am J Physiol Regulatory Integrative Comp Physiol, September 1, 1998; 275(3): R793 - R802. [Abstract] [Full Text] [PDF]

				V. Martinez, E. Barquist, J. Rivier, and Y. Tache Central CRF inhibits gastric emptying of a nutrient solid meal in rats: the role of CRF2 receptors Am J Physiol Gastrointest Liver Physiol, May 1, 1998; 274(5): G965 - G970. [Abstract] [Full Text] [PDF]

Central Injection of a New Corticotropin-Releasing Factor (CRF) Antagonist, Astressin, Blocks CRF- and Stress-Related Alterations of Gastric and Colonic Motor Function1

Central Injection of a New Corticotropin-Releasing Factor (CRF) Antagonist, Astressin, Blocks CRF- and Stress-Related Alterations of Gastric and Colonic Motor Function¹

				V. MartInez, F. Cuttitta, and Y. Tache Central Action of Adrenomedullin to Inhibit Gastric Emptying in Rats Endocrinology, September 1, 1997; 138(9): 3749 - 3755. [Abstract] [Full Text] [PDF]

				S. V. Coutinho, P. M. Plotsky, M. Sablad, J. C. Miller, H. Zhou, A. I Bayati, J. A. McRoberts, and E. A. Mayer Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat Am J Physiol Gastrointest Liver Physiol, February 1, 2002; 282(2): G307 - G316. [Abstract] [Full Text] [PDF]