Interaction of adenine nucleotides, UTP and suramin in mouse vas deferens: suramin-sensitive and suramin-insensitive components in the contractile effect of ATP

Abstract

Effects of various nucleotides, nucleosides and noradrenaline on smooth muscle tension were studied in the isolated mouse vas deferens. alpha, beta-Methylene-ATP, ATP gamma S, noradrenaline, ATP and UTP elicited contraction, with potency decreasing in that order; there was no contractile response to adenosine or uridine (up to 100 mumol/l). Prolonged incubation with alpha, beta-methylene-ATP (concentration increased stepwise from 0 to 15 mumol/l) selectively reduced contractions induced by ATP and UTP but not those induced by noradrenaline, and there was cross-tachyphylaxis between ATP and UTP. Suramin (10-300 mumol/l) did not alter the response to noradrenaline but shifted the concentration-response curves for alpha, beta-methylene-ATP, ATP gamma S, UTP and lower concentrations of ATP (0.1-1 mumol/l) to the right. The pA2-values of suramin were 5.2 against alpha, beta-methylene-ATP, 4.8 against ATP gamma S, 5.1 against UTP and 5.4 against lower concentrations of ATP. The effects of higher concentrations of ATP were largely resistant to suramin. The results indicate that the mouse vas deferens possesses contraction-mediating smooth muscle P2x-receptors. UTP also acts at this receptor, and there is no evidence for a separate UTP receptor. The selective inhibition of nucleotide- but not noradrenaline-induced contractions by suramin confirms the view that suramin is a selective P2-antagonist. The resistance against suramin of part of the effect of ATP suggests that ATP activates a suramin-insensitive site in addition to the P2x-receptor.