The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Jun 1995
mu-, delta- and kappa-opiate receptors mediate antinociception in the rat tail flick test following noxious thermal stimulation of one hindpaw.
Experiments were performed to investigate the possible involvement of spinal mu-, delta- and kappa-opiate receptors in mediating the antinociceptive effects of noxious thermal stimulation of one hindpaw on the tail flick reflex in the rat. Male Sprague-Dawley rats were implanted with chronic intrathecal catheters to the lumbar level of the spinal cord. After 5 to 7 days, they were lightly anesthetized with an i.p. injection of a mixture of Na-pentobarbital (20 mg/kg) and chloral hydrate (120 mg/kg). ⋯ In animals pretreated with CSF intrathecally 10 min before the stimulus, an increase in tail flick reaction time was observed peaking at 30 sec after the stimulus. This response was attenuated in a dose-related manner by preadministration of the specific mu-opiate receptor antagonist, beta-funaltrexamine, the specific delta-opiate receptor antagonist, H-Tyr-Tic psi[CH2NH]-Phé-Phe-OH or the specific kappa-opiate receptor antagonist, nor-binaltorphimine. The data show that the antinociceptive effect on the tail withdrawal reflex from a brief noxious thermal stimulus is provoked heterosegmentally by the noxious conditioning stimulus to the hindpaw and is mediated by the endogenous release of ligands that bind to mu-, delta- and kappa-opiate receptors in the spinal cord.
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J. Pharmacol. Exp. Ther. · Jun 1995
Effects of the bradykinin B2 receptor antagonist S 16118 (p-guanidobenzoyl-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin) in different in vivo animal models of inflammation.
The effects of S 16118 (p-guanidobenzoyl-[Hyp3,Thi5,D-Tic7, Oic8]bradykinin (BK)], a new, potent and long-acting BK B2 antagonist, were tested in some in vivo models of inflammation. In rats, S 16118 (0.1 and 1 mg/kg) given i.v. or s.c. delayed the edema formation induced by intraplantar carrageenan injections up to 4 hr after administration, confirming the involvement of kinins in this inflammatory reaction. In guinea pigs treated with atropine, vagal stimulation induced bronchial microvascular leakage. ⋯ In mice, i.p. LPS (25 mg/kg) administration induced over 90% mortality in 96 hr. S 16118 (1 mg/kg x 4), given 30 min before LPS injection and 4, 8 and 24 hr after LPS injection, did not influence the mortality rate.(ABSTRACT TRUNCATED AT 250 WORDS)