6-Benzylaminopurine: a Plant Derived Cytokinin Inducing Positive Inotropism by P2-purinoceptors

Positive inotropic effects induced by 6-benzylaminopurine (6-BAP), kinetin and zeatin were studied in rat atria. The potency order observed was 6-BAP > or = kinetin > zeatin. Suramin, a P2-purinoceptor antagonist, inhibited the positive effect of 6-BAP suggesting the involvement of P2-purinoceptors in the positive effect of this cytokinin. In order to elucidate this point, 6-BAP was used against R-PIA (a P1-purinoceptor agonist) and ATP and UTP (both P2-purinoceptor agonists). 6-BAP did not influence negative inotropism by R-PIA whereas both nucleotides were inhibited after pretreatment with the cytokinin. LY 83583, an inhibitor of cGMP production, reduced the inotropic effect by cytokinin whereas L-NAME, an inhibitor of the L-arginine/nitric oxide pathway, did not influence the effect induced by 6-BAP. Indomethacin, an inhibitor of cyclooxygenase, and neomycin, an inhibitor of phospholipase C, did not significantly modify positive inotropism by 6-BAP. Verapamil, an inhibitor of L-type calcium channels, did not change the positive effect of 6-BAP while TMB-8 and dantrolene, two inhibitors of intracellular calcium release, reduced the increase of contractile tension induced by cytokinin. Our data on rat atria suggest that 6-BAP causes a positive inotropism through activation of P2-purinoceptors, involving modification of cGMP and of intracellular calcium.