The mechanical response of rat myometrium to adenosine triphosphate in Ca-free solution.

Abstract

The contractile response of the myometrial longitudinal muscle of pregnant and estrogen-treated rats to adenosine triphosphate (ATP) was investigated. ATP (10-5-4 .times. 10-3 M) added to Krebs solution caused a generation of spontaneous activity consisting of phasic contractions and an elevation of muscle tone in a dose-dependent manner. Effects of the "test solution" consisting of isotonic K, 4(mM) ATP, 4Mg, 1-20 EGTA, 20 tris(hydroxymethyl)aminomethan (Tris) maleate (pH 6.8) on the contractile response was then investigated. An initial phasic and a following tonic contraction was evoked by the application of the test solution, when applied after the equilibration of the muscle with Krebs solution. ATP was proved to be an agonist to evoke the Ca-free contraction. The phasic contraction was depressed when the muscle was incubated with Ca-free Krebs solution. The amplitude of the tonic contraction became progressively larger when application of the test solution was repeated. The amplitude was 15-70% as large as the tonic component of the K-contracture induced by 40 mM K. Theophylline (10 mM), 0.1 mM papaverine and 1 .mu.M isoprenaline nearly abolished, and 1 mM cAMP partly depressed the tonic contraction of K-contracture, whereas the tonic contraction induced by the test solution was unaffected. A calmodulin antagonist, W-7 (100 .mu.M) strongly suppressed both the K-contracture and the contraction induced by the test solution, whereas trifluoperazine (10-200 .mu.M) preferentially depressed the K-contracture. The tonic contraction induced by the test solution was strongly depressed when Mg was removed and 20 mM EDTA was applied. From these results, it is discussed that some Ca-independent process is involved in the generation of tonic component of Ca-free contraction developed by the application of the test solution.