Capsaicin-sensitive bronchopulmonary receptors with dual sensory-efferent function: mode of action of capsaicin antagonists.
It has been suggested that capsaicin-sensitive interoceptors subserve dual sensory-efferent function in sense of being sites not only for initiating sensory impulses but also for release of mediators. The efferent response of smooth muscle contraction to capsaicin was analyzed in vitro on the trachea and main bronchi of the guinea-pig. Tetrodotoxin-resistant neurogenic contraction of the trachea evoked by capsaicin was inhibited by pretreatment of the tissue with the mast cell depleting agent of compound 48/80. Pretreatment of the preparation with indomethacin or with antagonists of histamine and 5-HT caused no changes in the responses. Electrical field stimulation of the nerve fibres in the main bronchi induced prolonged capsaicin-sensitive bronchoconstriction. Participation of mast cells and particularly leukotrienes in the responses is suggested. Sensory effect and site of action of capsaicin and its antagonists at the pulmonary receptors were tested in vivo by recording the Bezold-Jarisch reflex in the rat. Ruthenium red (0.5-2 mg/kg i.v.) and resiniferatoxin (0.1 micrograms/kg i.v.) did not evoke the vagal reflex triad of bradycardia, fall in blood pressure and apnoea, but antagonized the effect of capsaicin. The cardiorespiratory reflex triad evoked by stimulation of the regenerative region of the receptors by veratridine was not inhibited by ruthenium red. Furthermore, bradycardia evoked by electrical stimulation of the vagal nerve remained unchanged after pretreatment of the rat with either ruthenium red or resiniferatoxin. It is suggested that capsaicin excites the generator region of the receptors. Ruthenium red and resiniferatoxin antagonize its effect at different sites of the capsaicin receptor coupled cation channel.
Szolcsányi
J
J
Department of Pharmacology, University Medical School Pécs, Hungary.
Barthó
L
L
Pethö
G
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001980:Bronchi; D016084:Bronchoconstriction / Q000187:drug effects*; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth; D051381:Rats; D011919:Rats, Inbred Strains; D012430:Ruthenium Red / Q000494:pharmacology*; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000502:physiology; D014132:Trachea; D014701:Veratridine / Q000494:pharmacology
D004224:Diterpenes; D012430:Ruthenium Red; D014701:Veratridine; C024353:resiniferatoxin; D002211:Capsaicin