Pertussis toxin reduces the antiadrenergic effect of 2-chloroadenosine on papillary muscle and the direct negative inotropic effect of 2-chloroadenosine on atrium.

2-Chloroadenosine reduced the contractile tension of guinea-pig atria directly, and inhibited the increase in tension produced by beta-adrenergic stimulation of guinea-pig papillary muscle. Both effects were reduced by 8-phenyltheophylline, a competitive antagonist at extracellular P1-purinoceptors. Treatment of guinea-pigs with pertussis toxin reduced the sensitivity of both atria and ventricles to 2-chloroadenosine. Atria were significantly affected after treatment with 125 micrograms/kg toxin, but not 100 micrograms/kg. 60 micrograms/kg toxin had no effect on the sensitivity of the ventricles, but 100 and 125 micrograms/kg significantly decreased the antiadrenergic effect of 2-chloroadenosine. We conclude that both the direct and antiadrenergic effects are mediated by an inhibitory guanine nucleotide binding protein.