SIMULTANEOUS MEASUREMENT OF CYCLOPENTYLADENOSINE-INDUCED CONTRACTION AND INTRACELLULAR CALCIUM IN BRONCHIAL RINGS FROM ALLERGIC RABBITS ANDITS ANTAGONISM

We reported previously that adenosine is a specific contractile agonis t 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 A(1) adenosine receptor agonist, in relation to the role of intra cellular calcium ([Ca++](i)) in airway smooth muscle of allergic rabbi ts in the presence and absence of extracellular calcium (Ca++). The ef fects of adenosine receptor antagonists theophylline (xanthine) and CG S-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 s mooth muscle was accompanied by a quantitative increase in [Ca++](i) i n the presence of extracellular Ca++. CGS-21680, an A(2) agonist, prod uced only marginal changes in force and [Ca++](i) compared with CPA. T he CPA-induced contraction as well as changes in [Ca++](i) were signif icantly inhibited by both antagonists at a concentration of 10(-7) M. CGS-15943 and theophylline changed the EC(50) values for the force fro m 1.1 x 10(-7) M to 2.3 x 10(-6) M and 7.0 x 10(-6) M, respectively. I n Ca++-free medium, CPA (10(-4) M) induced only a 15 to 20% contractio n compared with Ca++-containing medium. The changes in [Ca++](i) were also reduced accordingly. CGS-15943 significantly inhibited the CPA-in duced tension and changes in [Ca++](i), whereas theophylline failed to inhibit these responses. 3-Cyclopentyl-1,3-dipropylxanthine, an A(1)- specific and potent antagonist, also did not inhibit the CPA-induced f orce and [Ca++](i) in a separate set of experiments. The tertiary airw ay smooth muscle rings from age-matched normal rabbits did not respond to CPA and there was no detectable change in [Ca++](i). These data su ggest that the asthmatic airway smooth muscle contraction has both ext racellular Ca++-dependent and -independent components and the Ca++-ind ependent component is xanthine insensitive.