Actions of ATP and α,β‐methylene ATP on neuromuscular transmission and smooth muscle membrane of the rabbit and guinea‐pig mesenteric arteries

Abstract

In the rabbit mesenteric artery, adenosine triphosphate (ATP), showed two actions on the membrane potential of muscle cells: low concentrations (1-10 microM) hyperpolarized and high concentrations (greater than or equal to 50 microM) depolarized the membrane. Both changes in the potential were accompanied by increases in ionic conductance. In the rabbit mesenteric artery, alpha, beta-methylene ATP (MeATP), (greater than or equal to 30 nM) depolarized the muscle membrane at a lower concentration than ATP (greater than or equal to 50 microM), and increased the ionic conductance of the membrane. The depolarization induced by ATP was prevented by low concentrations of MeATP, but the hyperpolarization was retained. Furthermore, the hyperpolarization was not affected by theophylline (10 microM). In the guinea-pig mesenteric artery, ATP and MeATP depolarized and increased the ionic conductance of muscle membrane, but to depolarize the membrane, higher concentrations of both agents were required, compared to those in the rabbit mesenteric artery. In the mesenteric arteries from both species, perivascular nerve stimulation evoked excitatory junction potentials (e.j.ps). In both tissues, MeATP inhibited the amplitude of e.j.ps at lower concentrations than did ATP, and both agents had more potent inhibitory actions on rabbit than on guinea-pig. The inhibition of e.j.p. induced by low concentrations of these agents showed no relationship to depolarization, but the inhibition induced by high concentrations was paralleled by depolarization and increase in ionic conductance of the membrane. In the rabbit mesenteric artery, overflow of noradrenaline (NA) and its metabolite (3,4-dihydroxyphenylglycol; DOPEG) produced by perivascular nerve stimulation was examined. ATP (0.1 mM) but not MeATP (0.1 microM) reduced the overflow of NA, whereas both agents had no effect on the overflow of DOPEG. Exogenously applied high concentrations of NA (greater than or equal to 3 microM) depolarized the muscle membrane in both species. These NA-induced depolarizations were not affected by treatment with ATP or MeATP. It is concluded that, in the rabbit mesenteric artery, ATP is more likely to be involved in generation of e.j.ps than is NA. A similar interpretation in the guinea-pig mesenteric artery is complicated by the depolarization produced by high concentrations of ATP or MeATP.