Effects of adenosine A2 receptor agonists on the excitation of capsaicin-sensitive afferent sensory nerves in airway tissues.
We examined the effects of adenosine analogues on the asthmatic reactions induced by the stimulation of capsaicin-sensitive afferent sensory nerves. Intravenous (i.v.) injection of adenosine A2 receptor agonists, 5'-(N-ethylcarboxamido)-adenosine (NECA) and 2-[p-(carboxyethyl)-phenylethylamino]-5'-N-ethylcarboxamido-adenos ine (CGS 21,680), dose dependently inhibited capsaicin-induced guinea-pig bronchoconstriction (1-1000 nmol kg-1), whereas i.v. administration of the adenosine A1 receptor agonist, N6-cyclo-hexyladenosine (CHA), did not affect it (1000 nmol kg-1). Intratracheal injection of NECA (0.05-5 nmol site-1) and CGS 21,680 (0.05-5 nmol site-1) also reduced capsaicin-induced constriction in a dose-dependent manner. However, NECA (1000 nmol kg-1) failed to inhibit substance P-induced guinea-pig bronchoconstriction. NECA (1-1000 nmol kg-1) dose-dependently inhibited cigarette smoke-induced rat tracheal plasma extravasation, but not substance P-induced reaction. NECA (0.1-10 microM) and CGS 21,680 (10 microM) significantly blocked the capsaicin-induced release of substance P-like immunoreactivity from guinea-pig lung, whereas CHA (10 microM) had no effect. This evidence suggests that adenosine A2 receptors modulate negatively the excitation of capsaicin-sensitive afferent sensory nerves and substance P release from their endings in airway tissues.
Morimoto
H
H
Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Yamashita
M
M
Imazumi
K
K
Matsuda
A
A
Ochi
T
T
Seki
N
N
Mizuhara
H
H
Fujii
T
T
Senoh
H
H
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000704:Analysis of Variance; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000294:innervation; D016084:Bronchoconstriction / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D010627:Phenethylamines / Q000494:pharmacology*; D010947:Plants, Toxic; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology*; D012906:Smoke; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology; D014026:Nicotiana; D014132:Trachea / Q000187:drug effects
D010627:Phenethylamines; D018047:Receptors, Purinergic P1; D012906:Smoke; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D013373:Substance P; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; D000241:Adenosine; D002211:Capsaicin