Characterization of the adenosine receptors in the airways.
Adenosine causes bronchoconstriction both in vivo and in vitro in human asthmatics. In an in vivo rat model of adenosine-induced bronchoconstriction, the order of bronchoconstrictor potency of adenosine analogues was NECA = CPA > APNEA > CHA > R-PIA > CGS21680. This order of potency does not fit with the classical order of potency for a single subtype of adenosine receptors. The complete lack of bronchoconstrictory activity of CGS21680 suggests, nevertheless, that the A2A receptor subtype is not involved in the adenosine-induced bronchoconstriction. A remarkable finding was the dose-response curve to APNEA, which is thought to have some selective activity on the A3 receptor. The A2A-selective antagonist KF17837 (10(-7) to 10(-5) mol/kg) had no significant inhibitory activity on the adenosine-induced bronchoconstriction. The A1 antagonists, KF15372 and KW3902, both significantly inhibited the NECA-induced bronchoconstriction in BDE rats. We, therefore, conclude that the adenosine-induced bronchoconstriction in the rat is most likely due to binding of adenosine to different receptor subtypes including the A1, A2B and A3 subtypes.
Pauwels
R A
RA
Department of Respiratory Diseases, University Hospital Ghent, Belgium.
Joos
G F
GF
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001285:Atropine / Q000494:pharmacology; D001667:Binding, Competitive; D016084:Bronchoconstriction / Q000502:physiology; D004195:Disease Models, Animal; D008168:Lung / Q000187:drug effects; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012143:Respiratory Physiological Phenomena; D014665:Vasodilator Agents / Q000494:pharmacology*
D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D019830:Adenosine-5'-(N-ethylcarboxamide); D001285:Atropine; D000241:Adenosine; D008784:Methysergide