Desflurane induces airway contraction mainly by activating transient receptor potential A1 of sensory C-fibers.
We previously reported that desflurane induced airway contraction via antidromic tachykinin release from sensory C-fibers. Here, we investigated the effect of desflurane on airway lung resistance (R(L)) using specific receptor antagonists in C-fibers. Young guinea pigs were anesthetized and their tracheas were cannulated with an endotracheal tube via a tracheotomy. A Fleisch pneumotachograph and a differential transducer were used to monitor respiratory flow rate, intrapleural pressure, and airway pressure, and R(L) was calculated and recorded. A transient receptor potential A1 (TRPA1) or a transient receptor potential V1 (TRPV1) selective antagonist of sensory C-fibers, i.e., HC030031 or BCTC, was administered before the exposure to desflurane. In an additional experiment, tachykinin receptor of airway smooth muscles was antagonized only by the neurokinin-2 receptor antagonist MEN-10376 before the exposure to desflurane. HC030031 completely inhibited both the first and the second contractile responses induced by desflurane, whereas BCTC had little effect. MEN-10376 also significantly and substantially diminished the contractile response. Desflurane contracts the airway in untreated guinea pigs mainly by activating irritant gas receptor TRPA1 of afferent C-fibers, resulting in the release of contractile tachykinins such as neurokinin A.
Satoh
Jun-ichi
J
Department of Anesthesiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
Yamakage
Michiaki
M
D000403:Airway Resistance / Q000187:drug effects*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000077335:Desflurane; D006168:Guinea Pigs; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects*; D018041:Receptors, Neurokinin-2 / Q000187:drug effects; D011984:Sensory Receptor Cells / Q000187:drug effects*; D050052:TRPC Cation Channels / Q000187:drug effects*; D015320:Tachykinins / Q000378:metabolism
D018685:Anesthetics, Inhalation; D018041:Receptors, Neurokinin-2; D050052:TRPC Cation Channels; D015320:Tachykinins; C096351:transient receptor potential cation channel, subfamily C, member 1; D000077335:Desflurane; D007530:Isoflurane