The effect of ATP analogues on the spontaneous electrical and mechanical activity of rat portal vein longitudinal muscle

Abstract

The effects of ATP (30–1 000 μM) and four of its structural analogues 2-methylthio ATP (30–1 000 μM), β, γ-methylene ATP (30–1 000 μM) (β, γ-MeATP), L-β, γ-methylene ATP (1–100 μM) (L-β, γ-MeATP) and α,β-methylene ATP (0.3–100 μM) (α, β-MeATP) were studied on the spontaneous electrical and mechanical activity of the longitudinal muscle of the rat portal vein using the sucrose gap apparatus. Portal vein preparations displayed spontaneous activity in which slow depolarizations led to bursts of spikes which were concomitant with rhythmic contractions. Low concentrations of ATP analogues initiated an increased frequency of the regular spontaneous waves of depolarizations and contractions. Higher concentrations caused an increased frequency of action potential firing, a sustained depolarization and contraction. The rank order of agonist potency for both contractile and electrophysiological responses was found to be α, β-MeATP > L-β, γ-MeATP > β, γ-MeATP > 2-methylthio ATP > ATP. Prolonged superfusion with α, β-MeATP (10 μM) led to desensitization of P 2-purinoceptors so that responses to the other ATP analogues were blocked while responses to noradrenaline were unaffected. On the basis of the rank order of agonist potencies and desensitization with α, β-MeATP, the P 2-purinoceptors mediating contraction of the longitudinal muscle of the rat portal vein are classified as being of the P 2X-subtype.