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Analysis of the role of endothelin-A and endothelin-B receptors on nociceptive information transmission in the spinal cord with FR139317, an endothelin-A receptor antagonist, and sarafotoxin S6c, an endothelin- B receptor agonist

T Yamamoto, N Shimoyama, H Asano and T Mizuguchi

Department of Anesthesiology, School of Medicine, Chiba University, Japan.

Endothelin (ET)-A and ET-B receptors have been reported to exist in the spinal cord but the roles of ET-A and ET-B receptors in the spinal cord are poorly understood. To gain a better understanding of the roles of ET-A and ET-B receptors in nociceptive information transmission in the spinal cord, this study evaluated the effects of ET-1, ET-3, Sarafotoxin S6c (an ET-B receptor-selective agonist) and (R)2-[(R)-2- [(S)-2-[[1- (hexahydro-1H-azepinyl)]carbonyl]amino-4-methyl- pentanoyl]amino-3- [3-(1-methyl-1H-indolyl)]propionyl]amino-3-(2- pyridyl)propionic acid (FR139317, an ET-A receptor-selective antagonist) on the agitation behavior evoked by formaldehyde solution injection and on the thermal nociceptive test. The s.c. injection of formaldehyde solution into the hind paw evoked a biphasic flinching (phase 1, 0-9 min; phase 2, 10-60 min) of the injected paw. For the purpose of data analysis, phase 2 was further divided into two phases (phase 2a, 10-34 min; phase 2b, 35-60 min). Intrathecal injection of ET- 1 depressed the phase 1 and 2 flinching behavior in a dose-dependent manner and this ET-1 effect was antagonized by FR139317. Intrathecal injection of either ET-3 or Sarafotoxin S6c enhanced the phase 2a flinching behavior in a dose-dependent manner. Intrathecal injection of the highest doses of ET-1, ET-3 and Sarafotoxin S6c had no effect on the thermal nociceptive test. These data indicate that ET-A and ET-B receptors have a powerful effect on spinal nociceptive processing evoked by formaldehyde solution injection but not that evoked by thermal stimulation.

Volume 271, Issue 1, pp. 156-163, 10/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1994 by the American Society for Pharmacology and Experimental Therapeutics.