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 x 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, 4 Mg, 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 µM 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 µM) strongly suppressed both the Kcontracture and the contraction induced by the test solution, whereas trifluoperazine (10-200 /LM) 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.

Effects of cytochalasins on the mechanical and membrane responses in the isolated longitudinal myometrium of pregnant rat with reference to the EGTA-resistant contraction.

“…It was reported that W-7, a calmodulin antagonist , strongly inhibited the EGTA-resistant contraction (ASHOORI et al, 1985;OsA and MARUTA, 1987a) .…”

The mechanical response of the isolated longitudinal muscle of pregnant rat myometrium to adenosine triphosphate in the Ca-free solution containing various polyvalent cations.

“…3). It was shown in the previous report that the ATP-induced contraction was depressed when the external Mg was omitted and EDTA was added (OsA and MARUTA, 1987). Thus, a view that Mg was stored in some store site of membrane, and released in the cell by ATP application is favored for the ATPinduced contraction.…”

“…In these circumstances, the contractile responses to ATP could result from a certain mechanism which increases the polyvalent cation in the cell, such as receptor-operated intracellular changes in cyclic nucleotides which in turn affect ionic fluxes of the membrane (KRALL and MORIN, 1986), changes in function of sarcoplasmic reticulum (KRALL et al, 1983), and regulation of actomyosin interaction (HARTSHORNE and SIEMANKOWSKI, 1981). It was shown that 10 mM theophylline, 0.1 mM papaverine, and 1 mM dibutyryl cyclic AMP did not cause a relaxation of the ATP-induced contraction in Ca-free solution, while these agents relaxed the K-contracture (OsA and MARUTA, 1987). ATP increases the amount of intracellular cyclic GMP in the thoracic aorta (RAPOPORT et al, 1984).…”

“…When the external Mg was removed from the solution, the Ca-free contraction was depressed. Therefore, a possibility that the Mg-influx was responsible for the generation of the tonic component of Ca-free contraction was suggested (OSA and MARUTA, 1987). In the present experiment, we attempted to delineate a more detailed feature of the ATP-induced contraction in the Ca-free solution generated in the longitudinal muscle of pregnant rat myometrium.…”

“…Adenosine triphosphate (ATP) is known to induce potentiation of membrane excitability in pregnant mouse myometrium (NINOMIYA and SUzuKI, 1983), and to potentiate contraction in the longitudinal muscle of pregnant rat myometrium (WATTS, 1953;OSA and MARUTA, 1987). ATP could also generate a contraction of rat myometrium in the Ca-free solution containing 4 mM Mg and 1-20mM EGTA.…”