Simultaneous measurement of cyclopentyladenosine-induced contraction and intracellular calcium in bronchial rings from allergic rabbits and it's antagonism.
We reported previously that adenosine is a specific contractile agonist in the asthmatic airways of allergic rabbits; cyclopentyladenosine (CPA) was the most potent bronchoconstrictor in this model. The aim of the present investigation was to examine the contracting effect of CPA, an A1 adenosine receptor agonist, in relation to the role of intracellular calcium ([Ca++]i) in airway smooth muscle of allergic rabbits in the presence and absence of extracellular calcium (Ca++). The effects of adenosine receptor antagonists theophylline (xanthine) and CGS-15943 (nonxanthine) were also evaluated on these responses. CPA (10(-9)-10(-4) M) produced a dose-dependent contraction of tertiary airway smooth muscle of allergic rabbits. An increase in tension of airway smooth muscle was accompanied by a quantitative increase in [Ca++]i in the presence of extracellular Ca++. CGS-21680, an A2 agonist, produced only marginal changes in force and [Ca++]i compared with CPA. The CPA-induced contraction as well as changes in [Ca++]i were significantly inhibited by both antagonists at a concentration of 10(-7) M. CGS-15943 and theophylline changed the EC50 values for the force from 1.1 x 10(-7) M to 2.3 x 10(-6) M and 1.0 x 10(-6) M, respectively. In Ca(++)-free medium, CPA (10(-4) M) induced only a 15 to 20% contraction compared with Ca(++)-containing medium. The changes in [Ca++]i were also reduced accordingly. CGS-15943 significantly inhibited the CPA-induced tension and changes in [Ca++]i whereas theophylline failed to inhibit these responses. 8-Cyclopentyl-1,3-dipropylxanthine, an A1-specific and potent antagonist, also did not inhibit the CPA-induced force and [Ca++]i in a separate set of experiments. The tertiary airway smooth muscle rings from age-matched normal rabbits did not respond to CPA and there was no detectable change in [Ca++]i. These data suggest that the asthmatic airway smooth muscle contraction has both extracellular Ca(++)-dependent and -independent components and the Ca(++)-independent component is xanthine insensitive.
Ali
S
S
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina, USA.
Metzger
W J
WJ
Mustafa
S J
SJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011817:Rabbits; D013806:Theophylline / Q000494:pharmacology
C048599:N(6)-cyclopentyladenosine; D013806:Theophylline; D000241:Adenosine; D002118:Calcium