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-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.
Manzini
S
S
Istituto Farmacobiologico Malesci S.p.A., Pharmacology Department, Florence, Italy.
Ballati
L
L
D015762:2-Chloroadenosine / Q000494:pharmacology*; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000758:Anesthesia; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D004351:Drug Resistance; D006168:Guinea Pigs; D007288:Inosine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000187:drug effects; D012701:Serotonin / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology*
D011983:Receptors, Purinergic; D015762:2-Chloroadenosine; D010660:Phenylisopropyladenosine; D012701:Serotonin; D019830:Adenosine-5'-(N-ethylcarboxamide); D007288:Inosine; D001285:Atropine; D000241:Adenosine; D002211:Capsaicin