Hypersensitivity of pulmonary C fibers induced by adenosine in anesthetized rats.
Compelling clinical evidence implicates the potential role of adenosine in development of airway hyperresponsiveness and suggests involvement of pulmonary sensory receptors. This study was carried out to determine the effect of a low dose of adenosine infusion on sensitivity of pulmonary C-fiber afferents in anesthetized open-chest rats. Infusion of adenosine (40 microg x kg-1x min-1 i.v. for 90 s) mildly elevated baseline activity of pulmonary C fibers. However, during adenosine infusion, pulmonary C-fiber responses to chemical stimulants and lung inflation (30 cmH2O tracheal pressure) were markedly potentiated; e.g., the response to right atrial injection of capsaicin (0.25 or 0.5 microg/kg) was increased by more than fivefold (change in fiber activity = 2.64 +/- 0.67 and 16.27 +/- 3.11 impulses/s at control and during adenosine infusion, n = 13, P < 0.05), and this enhanced response returned to control in approximately 10 min. The potentiating effect of adenosine infusion was completely blocked by pretreatment with 8-cyclopentyl-1,3-dipropylxanthine (100 microg/kg), a selective antagonist of the adenosine A1 receptor, but was not affected by 3,7-dimethyl-1-propargylxanthine (1 mg/kg), an A2-receptor antagonist, or 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (2 mg/kg), an A3-receptor antagonist. This potentiating effect was also mimicked by N6-cyclopentyladenosine (0.25 microg x kg-1 x min-1 for 90 s), a selective agonist of the adenosine A1 receptor. In conclusion, our results showed that infusion of adenosine significantly elevated the sensitivity of pulmonary C-fiber afferents in rat lungs and that this potentiating effect is likely mediated through activation of the adenosine A1 receptor.
Gu
Qihai
Q
Department of Physiology, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA.
Ruan
Ting
T
Hong
Ju-Lun
JL
Burki
Nausherwan
N
Lee
Lu-Yuan
LY
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001835:Body Weight / Q000502:physiology; D001919:Bradycardia / Q000139:chemically induced / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D008168:Lung / Q000294:innervation*; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000187:drug effects; D018047:Receptors, Purinergic P1 / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology
D043682:Receptor, Adenosine A1; D018047:Receptors, Purinergic P1; D014970:Xanthines; C048599:N(6)-cyclopentyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D002211:Capsaicin