alpha,beta-MeATP augments the UTP contraction of rabbit basilar artery

The mechanism underlying the interaction between alpha,beta-methyleneadenosine 5'-triphosphate (alpha,beta-MeATP) and uridine 5'-triphosphate (UTP) was investigated using the basilar artery of a rabbit. UTP induced a concentration-dependent contraction, whereas P2X receptor agonists, such as alpha,beta-MeATP and 2-methylthioadenosine 5'-triphosphate (2-MeSATP), did not induce any contraction up to 100 microM. alpha,beta-MeATP augmented the UTP contraction two-fold, immediately and reversibly. This effect was observed with ectonucleotidase inhibition with 1 mM Ni(2+), the removal of extracellular Ca(2+) or Evans blue. The contractile response to adenosine 5'-O-(3-triphosphate) (ATPgammaS), a selective agonist for P2Y(4), was augmented by pretreatment with alpha,beta-MeATP also. ATPgammaS had no additional effect on the UTP contraction fully activated with alpha,beta-MeATP. UTP (100 microM) did not induce an increase in cytosolic Ca(2+) in a rabbit basilar arterial strip; however, in the presence of 1 mM alpha,beta-MeATP, UTP induced a significant increase in cytosolic Ca(2+). These results suggest that alpha,beta-MeATP facilitates the activation by UTP of the P2Y receptor (P2Y(4)) of the rabbit basilar artery through mechanisms other than nucleotidase inhibition, and that it does not do so via a P2X receptor.