α,β-MeATP augments the UTP contraction of rabbit basilar artery

Abstract

The mechanism underlying the interaction between α,β-methyleneadenosine 5′-triphosphate (α,β-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 α,β-MeATP and 2-methylthioadenosine 5′-triphosphate (2-MeSATP), did not induce any contraction up to 100 μM. α,β-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) (ATPγS), a selective agonist for P2Y 4, was augmented by pretreatment with α,β-MeATP also. ATPγS had no additional effect on the UTP contraction fully activated with α,β-MeATP. UTP (100 μM) did not induce an increase in cytosolic Ca 2+ in a rabbit basilar arterial strip; however, in the presence of 1 mM α,β-MeATP, UTP induced a significant increase in cytosolic Ca 2+. These results suggest that α,β-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.