Capsaicin desensitization selectively inhibits lipoxin A4-induced contraction in guinea pig bronchus.
The pharmacological ablation of capsaicin-sensitive afferents by means of capsaicin desensitization is usually utilized as a first functional criterion to identify substances whose biological effects might involve activation of this type of nerves. We have studied, in guinea pig epithelium-denuded bronchial rings (in the presence of the neutral endopeptidase inhibitor thiorphan), the effect of in vitro capsaicin desensitization (10 microM for 15 min) on bronchomotor responses elicited by leukotriene D4 (10-100 nM), 15-HETE (3-6 microM) and lipoxin A4 (3-6 microM). While all these three lipid mediators contract bronchial preparations, only lipoxin A4 effects were markedly depressed by previous capsaicin challenge. As expected, capsaicin desensitization abolished subsequent motor responses to capsaicin itself or stimulation of non-adrenergic non-cholinergic nerves, while it left unaffected cholinergic responses. It is proposed that endogenously-generated lipoxin A4 acts, at least partially, through the activation of capsaicin-sensitive sensory nerve fibers.
Manzini
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Istituto Farmacobiologico Malesci S.p.A., Pharmacology Department, Florence, Italy.
Meini
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D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D004361:Drug Tolerance; D004558:Electric Stimulation; D006168:Guinea Pigs; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D044045:Lipoxins; D008297:Male; D009119:Muscle Contraction; D013189:SRS-A / Q000494:pharmacology
D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D013189:SRS-A; C040527:lipoxin A4; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D002217:Carbachol; D002211:Capsaicin