2‐Chloroadenosine induction of vagally‐mediated and atropine‐resistant bronchomotor responses in anaesthetized guinea‐pigs

1 The bronchoconstrictor effects of intravenous administration of adenosine derivatives in anaesthetized non‐curarized guinea‐pigs have been studied. 2 2‐Chloroadenosine (2‐Cl‐Ade), 5′‐N‐ethylcarboxamideadenosine (NECA) and l ‐N 6 ‐phenylisopropyl‐adenosine ( l ‐PIA) all produced dose‐dependent, transient increases in tracheal insufflation pressure, with an order of potency (NECA ≤ 2‐Cl‐Ade ≫ l ‐PIA) typical of A 2 ‐receptor mediated biological responses. 3 2‐Chloroadenosine‐induced bronchoconstrictor responses disappeared after vagotomy or topical application of tetrodotoxin (TTX) on cervical vagal trunks. 4 2‐Chloradenosine‐induced bronchospasm was unaffected by atropine (1 mg kg −1 i.v.), physostigmine (50 μg kg −1 i.v.) and hexamethonium (30 mg kg −1 i.v.) but was significantly reduced by theophylline (25 mg kg −1 i.v.). 5 The magnitude of 2‐Cl‐Ade‐induced bronchospasm was significantly reduced by acute (10 μg kg −1 i.v.) or chronic (55 mg kg −1 s.c. four days before the experiment) pretreatment with capsaicin. 6 Guanethidine (20 mg kg −1 s.c. on two consecutive days), prazosin (10 μg kg −1 i.v.), diphenhydramine (1 mg kg −1 i.v.) and indomethacin (1 mg kg −1 i.v.) failed to block the bronchomotor response to 2‐Cl‐Ade. In contrast, cyproheptadine (1–5 mg kg −1 i.v.) markedly reduced, but did not abolish the bronchospasm elicited by the purine derivative. 7 We conclude that in anaesthetized non‐curarized guinea‐pigs, a transient vagally‐mediated bronchospasm can be induced by stimulation of A 2 ‐purinoceptors. This effect is complex and involves, at least in part, stimulation of capsaicin‐sensitive sensory nerves and 5‐hydroxytryptamine release. This experimental model might be useful for the further study of the potential role of adenosine in asthma, and for the evaluation of new antiasthma drugs.