Involvement of A1 adenosine receptors and neural pathways in adenosine-induced bronchoconstriction in mice.
High levels of adenosine can be measured from the lungs of asthmatics, and it is well recognized that aerosolized 5'AMP, the precursor of adenosine, elicits robust bronchoconstriction in patients with this disease. Characterization of mice with elevated adenosine levels secondary to the loss of adenosine deaminase (ADA) expression, the primary metabolic enzyme for adenosine, further support a role for this ubiquitous mediator in the pathogenesis of asthma. To begin to identify pathways by which adenosine can alter airway tone, we examined adenosine-induced bronchoconstriction in four mouse lines, each lacking one of the receptors for this nucleoside. We show, using direct measures of airway mechanics, that adenosine can increase airway resistance and that this increase in resistance is mediated by binding the A(1) receptor. Further examination of this response using pharmacologically, surgically, and genetically manipulated mice supports a model in which adenosine-induced bronchoconstriction occurs indirectly through the activation of sensory neurons.
Hua
Xiaoyang
X
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7219, USA.
Erikson
Christopher J
CJ
Chason
Kelly D
KD
Rosebrock
Craig N
CN
Deshpande
Deepak A
DA
Penn
Raymond B
RB
Tilley
Stephen L
SL
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects; D009434:Neural Pathways / Q000378:metabolism*; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D012137:Respiratory System / Q000166:cytology / Q000187:drug effects; D014628:Vagotomy
D043682:Receptor, Adenosine A1; D019830:Adenosine-5'-(N-ethylcarboxamide); D000241:Adenosine