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 greater than or equal to kinetin > zeatin. Suramin, a PZ-purinoceptor antag onist, inhibited the positive effect of 6-BAP suggesting the involvement of PZ-purinoceptors in the positive effect of this cytokinin. In order to elu cidate this point, 6-BAP was used against R-PIA (a P1-purinoceptor agonist) and ATP and UTP (both PZ-purinoceptor agonists). 6-BAP did not influence n egative inotropism by R-PIA whereas both nucleotides were inhibited after p retreatment with the cytokinin. LV 83583, an inhibitor of cGMP production, reduced the inotropic effect by cytokinin whereas L-NAME, an inhibitor of t he L-arginine/nitric oxide pathway, did not influence the effect induced by 6-BAP. Indomethacin, an inhibitor of cyclooxygenase, and neomycin, an inhi bitor of phospholipase C, did not significantly modify positive inotropism by 6-BAP. Verapamil, an inhibitor of L-type calcium channels, did not chang e the positive effect of 6-BAP while TMB-8 and dantrolene, two inhibitors o f intracellular calcium release, reduced the increase of contractile tensio n induced by cytokinin. Our data on rat atria suggest that 6-BAP causes a p ositive inotropism through activation of P2-purinoceptors, involving modifi cation of cGMP and of intracellular calcium.