Pre‐ and post‐junctional effects of adenosine triphosphate on noradrenergic transmission in the rabbit ear artery.

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Abstract
1. The effects of adenosine triphosphate (ATP), 5''-adenylylimidodiphosphate (AMP-PNP) or .alpha.,.beta.-methylene ATP (mATP) on the excitatory junction potential (e.j.p.) and slow depolarization evoked by perivascular nerve stimulation were studied in smooth muscle cells of the rabbit ear artery. 2. ATP (above 10-6 M), AMP-PNP (above 10-6M) and mATP (above 10-8M) transiently (10-15 min) depolarized the membrane. The membrane remained depolarized after prolonged exposure (over 20 min) to ATP (above 3 .times. 10-5 M), AMP-PNP (above 10-5 M) or mATP (above 3 .times. 10-8 M). 3. ATP (above 10-5 M), AMP-PNP (above 5 .times. 10-6 M) or mATP (above 3 .times. 10-8 M) decreased the membrane resistance. Increasing the external K+ concentration (Ko+) to 10 .cntdot. 1 mM also decreased the membrane resistance, with an associated depolarization. 4. ATP (10-6-5 .times. 10-5M) or AMP-PNP (over 10-6 M) transiently decreased and then increased amplitudes of the e.j.p. and of the slow depolarization, the latter component increasing more than the former. 5. Depolarization of the membrane by 10 .cntdot. 1 mM-Ko+ solution or mATP (10-7 M) decreased the amplitude of e.j.p.s, with no change in the facilitation, and the slope of the relationship between amplitude of e.j.p. and that of slow depolarization decreased with mATP but not with 10 .cntdot. 1 mM-Ko+ solution. 6. The outflows of noradrenaline and 3,4-dihydroxyphenylglycol (DOPEG) induced by perivascular nerve stimulation increased with ATP (above 10-6 M) or AMP-PNP (above 10-5 M), while there was no change with mATP (10-8-10-5 M) or 10 .cntdot. 1 mM-Ko+ solution. 7. Pre-treatment with mATP inhibited the ATP-induced increase in the outflow of noradrenaline and DOPEG, and also the ATP-induced enhancement of the amplitude of the e.j.p. 8. Therefore ATP and AMP-PNP have predominantly excitatory actions on both pre- and post-junctional membranes, while mATP has an excitatory action on the post-junctional membrane but antagonizes the facilitatory action of ATP on release of noradrenaline from the nerve terminal.