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

Abstract

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-N6-phenylisopropyl-adenosine (L-PIA) all produced dose-dependent, transient increases in tracheal insufflation pressure, with an order of potency (NECA greater than or equal to 2-Cl-Ade much greater than L-PIA) typical of A2-receptor mediated biological responses. 3. 2-Chloradenosine-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 micrograms 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 micrograms kg-1 i.v.) or chronic (55 mgkg-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 micrograms 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 mgkg-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 A2-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.