Effects of adenosine on NANC bronchoconstriction in anaesthetized guinea-pigs
Nieri, P.; Martinotti, L.; Lazzeri, N.; Breschi, M.C.
Journal of Pharmacy and Pharmacology 48(4): 422-428
1996
ISSN/ISBN: 0022-3573 PMID: 8794995 Document Number: 455856
The present work assesses the effects of the acute administration of adenosine on tachykinergic bronchoconstriction induced in different ways (exogenously administered capsaicin or substance P and vagal electrical stimulation) in anaesthetized and curarized guinea-pigs. Adenosine (30-3000 mu-g kg-1, i.v.) enhanced significantly and dose-relatedly the airway narrowing induced by a single dose of capsaicin (0.5-2 mu-g kg-1, i.v.), both in normal and in vagotomized animals. A smaller and less dose-dependent enhancement by the nucleoside of the pulmonary resistance increase induced by substance P (5-15 mu-g kg-1, i.v.) was observed. This effect was almost completely prevented by the H-1 antagonist diphenhydramine (1 mg kg-1, i.v.), which also unmasked an inhibitory action of adenosine at the highest doses. Diphenhydramine, on the contrary, did not significantly modify the potentiation by adenosine of capsaicin-mediated bronchoconstriction. Finally, the nucleoside dose-dependently inhibited the atropine-resistant bronchospasm following vagal electrical stimulation. The use of the selective adenosinic agonists R-N-6-(2-phenylisopropyl)adenosine (1-100 mu-g kg-1, i.v.) and 5'-N-methylcarboxamidoadenosine (1-100 mu-g kg-1, i.v.) before the administration of capsaicin, revealed the ability of the first to reproduce the enhancement induced by adenosine, while the second had an inhibitory effect. It is concluded that adenosine has both excitatory and inhibitory modulatory effects on airway responsiveness to excitatory non-adrenergic non-cholinergic (e-NANC) stimuli. The excitatory effects, revealed with substance P and capsaicin, support the hypothesis that adenosine may play a role as an asthma mediator.