Activation of pulmonary C fibres by adenosine in anaesthetized rats: role of adenosine A1 receptors.
1. Intravenous administration of adenosine (Ado) to patients can cause dyspnoea, chest discomfort and bronchoconstriction. To assess the role of vagal pulmonary C fibres in evoking these adverse reactions, the effect of Ado on single pulmonary C fibres was studied in anaesthetized and artificially ventilated rats. 2. Right-atrial injection of Ado (320 microg kg-1) activated 68 % (73/107) of pulmonary C fibres; the total number of action potentials during a period of 15 s increased from a baseline of 0.2 +/- 0.1 impulses to a peak of 16.4 +/- 2.6 impulses (P < 0.01, n = 107) after Ado. Inosine, the metabolite of Ado, did not activate any of eleven C fibres tested in six rats. Furthermore, C fibres were activated only by right-atrial and not by left-ventricular injection of the same dose of Ado. 3. Unlike the immediate and transient stimulation of C fibres by capsaicin, the C fibre stimulation by Ado had a latency of 6.5 +/- 0.3 s (range, 3-18 s) and lasted longer. 4. The stimulation of C fibres by Ado was significantly attenuated by pretreatment with aminophylline, a non-selective Ado receptor antagonist, was completely prevented by 1,3-dipropyl-8-cyclopentylxanthine, an Ado A1 receptor antagonist, but was unaffected by 3,7-dimethy-1-propargylxanthine, an A2 receptor antagonist. None of these Ado receptor antagonists prevented capsaicin-induced C fibre stimulation. 5. In conclusion, Ado stimulates pulmonary C fibre terminals through an activation of A1 receptors. The stimulation of pulmonary C fibres may play an important role in Ado-induced adverse respiratory effects.
Hong
J L
JL
Department of Physiology, University of Kentucky, Lexington, KY 40536-0084, USA.
Ho
C Y
CY
Kwong
K
K
Lee
L Y
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D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000241:Adenosine / Q000494:pharmacology*; D000344:Afferent Pathways / Q000502:physiology; D000768:Anesthesia, General; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D007288:Inosine / Q000494:pharmacology; D008168:Lung / Q000294:innervation*; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology*; D012119:Respiration; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014132:Trachea / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; D007288:Inosine; C057837:3,7-dimethyl-1-propargylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D013805:Theobromine; D002211:Capsaicin