Comparison of the effects of apamin, a Ca2+-dependent K+ channel blocker, and arylazido aminopropionyl ATP (ANAPP3), a P2-purinergic receptor antagonist, in the guinea-pig vas deferens

Abstract

Apamin, which blocks Ca2+-dependent increases in K+ permeability, antagonizes ATP-induced relaxation of several smooth muscles. The ATP photoaffinity label arylazido aminopropionyl ATP (ANAPP3), following its photolysis in the presence of the guinea-pig vas deferens, antagonizes contractile responses to ATP. This study was conducted to determine whether apamin antagonizes ATP-induced responses in the guinea-pig vas deferens, and also to evaluate whether ANAPP3 antagonizes responses to ATP by interfering with Ca2+-dependent K+ permeability changes. Apamin (10(-6) M) potentiated ATP-induced contractions. This potentiation was nonspecific in that responses to norepinephrine, histamine and acetylcholine also were enhanced; responses to KCl were unaffected. To evaluate the possible interactions between the two agents at the same cellular site, the effect of apamin was examined in ANAPP3-treated tissues. In such tissues apamin did not potentiate the residual responses to ATP; however, apamin was nevertheless able to potentiate responses of ANAPP3-treated tissues to norepinephrine, histamine and acetylcholine, and responses to KCl remained unaffected. These studies provide additional support for the view that ANAPP3 antagonizes ATP-induced responses of the guinea-pig vas deferens by blocking P2-purinergic receptors. The antagonism by ANAPP3 is not attributable to a blockade of Ca2+-dependent K+ permeability changes.