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A new CysLT 1 and CysLT 2 receptors-mediated anaphylaxis guinea pig model.

Authors :: Sekioka T
Kadode M
Osakada N
Fujita M
Matsumura N
Yamaura Y
Nakade S
Nabe T
Kawabata K
Source :: Prostaglandins, leukotrienes, and essential fatty acids [Prostaglandins Leukot Essent Fatty Acids] 2017 Apr; Vol. 119, pp. 18-24. Date of Electronic Publication: 2017 Mar 08.
Publication Year :: 2017
Abstract: Although the effectiveness of CysLT <subscript>1</subscript> receptor antagonists on asthma has been clinically established, the effects of CysLT <subscript>2</subscript> receptor antagonists are still unclear. The purpose of this study was to develop a new CysLT <subscript>1</subscript> and CysLT <subscript>2</subscript> receptors-mediated anaphylaxis guinea pig model using S-hexyl GSH, a γ-glutamyl transpeptidase (GTP) inhibitor, to suppress conversion of LTC <subscript>4</subscript> to LTD <subscript>4</subscript> . Actively sensitized guinea pigs were challenged with OVA in the absence or presence of S-hexyl GSH, and survival rate following anaphylactic response was monitored. OVA-induced fatal anaphylaxis in the absence of S-hexyl GSH was almost completely inhibited by montelukast, a CysLT <subscript>1</subscript> receptor antagonist, but not by the CysLT <subscript>2</subscript> receptor antagonist BayCysLT <subscript>2</subscript> RA. However, under treatment with S-hexyl-GSH, the inhibitory effect of motelukast was dramatically diminished, whereas that of BayCysLT <subscript>2</subscript> RA was markedly increased. The dual CysLT <subscript>1/2</subscript> receptor antagonist ONO-6950 effectively inhibited anaphylactic response in both S-hexyl GSH-treated and non-treated animals. LC/MS/MS analysis revealed that S-hexyl GSH treatment actually inhibited LTC <subscript>4</subscript> metabolism in the blood and lung tissues. Using S-hexyl GSH, we developed a novel CysLT <subscript>1</subscript> and CysLT <subscript>2</subscript> receptors-mediated anaphylaxis guinea pig model that can be useful for not only screening both CysLT <subscript>2</subscript> and CysLT <subscript>1/2</subscript> receptors antagonists, but also for functional analysis of CysLT <subscript>2</subscript> receptors.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)