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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vanadate, 30 microM, contracts uterine smooth muscle of estrogen-dominated non-pregnant rats in Ca(2+)-free medium after preincubation with 3 mM EGTA. In spite of the phosphorylation of the myosin light chain during this contraction, studies with fura-2 suggested that this contraction was not accompanied by an increase in the cytosolic Ca2+ level. Inhibitors of the myosin light chain kinase and protein kinase C partly inhibited this contraction. Vanadate seems to enter the cell through anion channels to inhibit phosphatases, resulting in phosphorylation via basal activities of the myosin light chain kinase and protein kinase C. An increase in the cytosolic free Ca2+ level resulted in relaxation of the contracting muscle in the same manner as in the oxytocin-induced Ca(2+)-free contraction.
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PMID:Ca(2+)-independent contraction of uterine smooth muscle induced by vanadate and its inhibition by Ca2+. 142 86

Contraction of rat uterine smooth muscle related to phosphorylation state of myosin light chain under various conditions was investigated. In the Ca2(+)-containing medium, both high K+ and oxytocin induced marked contraction of the muscle accompanied by pronounced phosphorylation of myosin light chain. In the Ca2(+)-free medium, although both vanadate and oxytocin induced slight contraction, phosphorylation of myosin light chain was only evident for vanadate but not for oxytocin. It was suggested that another mechanism distinct from myosin light chain phosphorylation might be involved in Ca2(+)-independent contraction of uterine smooth muscle elicited by oxytocin.
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PMID:Oxytocin contracts rat uterine smooth muscle in Ca2(+)-free medium without any phosphorylation of myosin light chain. 190

Ca2+/calmodulin-dependent phosphorylation of the 20-kDa regulatory light chain of myosin is of signal importance in the initiation of contraction in a number of smooth muscle tissues. In this investigation, we evaluated the relationship between intracellular free Ca2+/concentration [( Ca2+]i) and the extent of myosin light chain phosphorylation in cultured human myometrial smooth muscle cells. Treatment of myometrial cells with ionomycin caused a concentration- and time-dependent increase in [Ca2+]i and phosphorylation of myosin light chain. Temporally, the increases in light chain phosphorylation and [Ca2+]i in response to ionomycin were similar. In myometrial cells treated with ionomycin (10(-5) M) for 10 s, [Ca2+]i increased from 138 to 800 nM; in these same cells, myosin light chain phosphorylation increased from 5% to a maximum value of 54%. Half-maximal phosphorylation of myosin light chain was attained at 300 nM [Ca2+]i. Treatment of myometrial smooth muscle cells with prostaglandin (PG) F2 alpha (10(-8) M) and PGE2 (10(-8) M) caused a proportionate increase in [Ca2+]i and myosin light chain phosphorylation. In addition, [Ca2+]i and myosin light chain phosphorylation increased in response to oxytocin and angiotensin II. These findings indicate that a number of uterotonic agents effect an increase in [Ca2+]i, which in turn causes phosphorylation of myosin light chain. Furthermore, the concentration of Ca2+ in the cytoplasm is a primary determinant for myosin light chain phosphorylation in human myometrial smooth muscle cells.
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PMID:Myosin light chain phosphorylation in human myometrial smooth muscle cells. 230 67

Stretching of rat uterine strips induced phosphorylation of the 20,000-Da light chain of myosin to the same extent as was observed in strips contracted by carbachol or oxytocin. Stretching also reversed the partial dephosphorylation of light chain caused by treatment with ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) for 1 min. However, complete dephosphorylation of the light chain with 50-min EGTA-treatment could not be reversed by stretch. When stretched uterine strips containing light chain with a phosphate content greater than 0.75 mol/mol were quick-released, active force developed. On the other hand, when the phosphate content of light chain was reduced to less than 0.25 mol/mol, quick-release of the stretched strips did not produce active force. It is shown that Ca2+ mobilized from intracellular sources is involved in stretch-induced phosphorylation. The data indicate that myosin light chain phosphorylation is a prerequisite for active force development in smooth muscle.
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PMID:Stretch-induced myosin light chain phosphorylation in rat uterus. 375 7

Oxytocin (10 nM) stimulated the phosphorylation of the 20,000 mol wt myosin light chain in rat mammary myoepithelial cells from a basal level of 0.17 to 0.85 mol phosphate/mol light chain within 30 sec. Of the smooth muscle stimulants tested, oxytocin appears to be the only normal physiological stimulus for myosin phosphorylation in these cells. The roles of cAMP, cGMP, and calcium ions were investigated in the mode of action of oxytocin and the regulation of myosin phosphorylation. Although oxytocin had no effect on cGMP metabolism, there was an increase in the cAMP content of the treated myoepithelial cells. Further investigation suggested that the increase in cAMP levels in response to oxytocin was not directly involved in the regulation of myosin phosphorylation. Various agents known to interfere with calcium ion transport were used to study the role of calcium ions in the action of oxytocin and the regulation of myosin phosphorylation. The results indicate that the duration of the cellular response to oxytocin depends on an influx of extracellular calcium through calcium-specific channels in the plasma membrane.
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PMID:Oxytocin-stimulated myosin phosphorylation in mammary myoepithelial cells: roles of calcium ions and cyclic nucleotides. 632 26

Computer image analysis programs developed by astronomers for celestial photometry were used for the analysis of autoradiographs of electrophoretic slab gels. Oxytocin-stimulated myosin light chain phosphorylation in mammary myoepithelial cells was studied by incubating cells with [32P]orthophosphate followed by oxytocin addition, polyacrylamide gel electrophoresis of cellular protein, and autoradiography of electrophoretic slab gels. After scanning and digitization of autoradiographs, [32P]phosphate incorporation into the myosin light chain was measured by the determination of radiation flux recorded on the X-ray film. Within seconds after oxytocin addition, the myosin light chain was fully phosphorylated. The large library of astronomical computer programs has applications for the quantitative analysis of both one- and two-dimensional electrophoretic gels.
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PMID:Determination of myosin light chain phosphorylation using astronomical image analysis programs on autoradiographs of electrophoretic gels. 685 89

The response of mammary myoepithelial cells to oxytocin was studied by monitoring the level of phosphorylation of the 20,000 mol wt light chain of myosin. Myoepithelial cells were obtained by collagenase dispersion of involuted rat mammary tissue. The cells were equilibrated with [32P]orthophosphate, and then stimulated with oxytocin. Phosphorylated proteins were separated by polyacrylamide gel electrophoresis, and incorporation of 32P into the proteins was detected by autoradiography. Nanomolar concentrations of oxytocin caused a 3-fold increase in the level of phosphorylation of the myosin light chain within 0.5 min. When the cells were incubated with oxytocin in a calcium-free medium, there was only a transient phosphorylation of myosin. However, readdition of calcium to these cells resulted in phosphorylation of the myosin light chain. The results suggest that calcium is involved in the intracellular events following stimulation of the cells with oxytocin.
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PMID:Phosphorylation of myosin in mammary myoepithelial cells in response to oxytocin. 707 45

Parturition results from the establishment of phasic regular uterine contractions. Contractility in myometrial smooth muscle is stimulated by an increase in intracellular calcium ([Ca2+i]) which activates myosin light chain phosphorylation leading to increased myosin ATPase activity and enhanced rate of acto-myosin cross bridge formation. G proteins play a pivotal role in smooth muscle activation and relaxation by coupling cell membrane receptors to effector enzymes and ion channels. G alpha(s) and G alpha(i) stimulate and inhibit adenylyl cyclase, respectively and control cAMP formation. G alpha(q) stimulates phospholipase C resulting in the formation of two second messengers: inositol 1,4,5-trisphosphate (InsP3) which releases Ca2+ from the sarcoplasmic reticulum, and 1,2-diacylglycerol which activates protein kinase C. The oxytocin receptor stimulates myometrial contractility by increasing [Ca2+i] through both pertussis toxin resistant (G alpha(q)) and pertussis toxin sensitive (?G alpha (i)) pathways. beta-Adrenoceptors and prostaglandin EP2 receptors promote relaxation via G alpha(s)-adenylyl cyclase. The concentration of myometrial oxytocin receptors is five-times higher in pregnant compared to non-pregnant myometrium but decreases in samples obtained during labour. When myometrial slices are challenged with oxytocin there is a rapid increase in InsP3 levels with a time course which is similar to the rise in [Ca2+i] provoked by oxytocin in cultured myometrial cells. The formation of InsP3 in response to oxytocin in myometrial tissue at term is similar in samples obtained before and after the onset of labour. G alpha(q) and G alpha(i) are expressed at similar levels in non-pregnant and in pregnant myometrium obtained before or during labour. By contract, G alpha(s) levels are higher in pregnant compared to non-pregnant myometrium and decrease in samples obtained during labor. These changes in G alpha(s) are paralleled by prostaglandin E2-induced adenylyl cyclase activity in the same tissues. Parturition may be the consequence of downregulation of pathways that favour uterine quiescence by increasing cAMP formation, resulting in a relative dominance of stimulatory receptors that increase InsP3/Ca2+ availability.
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PMID:Parturition: activation of stimulatory pathways or loss of uterine quiescence? 871 97

Upon stimulation with high K+, oxytocin, prostaglandin E2, prostaglandin F2 alpha or carbachol, myometrium isolated from pregnant rats (21 days after pregnancy) developed 2-3 times greater isometric force than that from non-pregnant rats (estrus). High K+ increased the level of myosin light chain (MLC) phosphorylation to a similar extent in these tissues, and therefore pregnant myometrium developed greater contraction than non-pregnant myometrium at a given MLC phosphorylation. In the permeabilized muscle with alpha-toxin, Ca2+ (0.1-10 microM) induced greater contraction in pregnant myometrium than in non-pregnant myometrium. Ca2+ sensitivity was not altered after pregnancy. MLC kinase and phosphatase activities did not differ significantly between pregnant and non-pregnant myometria. Stimulation with 10 microM Ca2+ and 1 microM calyculin-A elicited similar magnitudes of contractions in the permeabilized muscles isolated from non-pregnant and pregnant rats. SDS-PAGE showed that the percentage of the content of MLC was not altered between these preparations, although actin content increased after pregnancy. These results suggest that the stress generating capacity of myometrium is increased after pregnancy without changing the MLC phosphorylation step. The equal capacity of force generation after the maximum phosphorylation by Ca2+ and phosphatase inhibitor suggests that a MLC phosphorylation-independent mechanism is responsible for the development of greater force in the pregnant myometrium.
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PMID:Increased contractility of rat uterine smooth muscle at the end of pregnancy. 988 77

Oxytocin is commonly used to induce or augment labor, but its mode of action is uncertain. To address the issue, isometric tension and the intracellular free Ca2+ concentration ([Ca2+]i) were simultaneously recorded from isolated strips of pregnant human myometrium loaded with fura 2. The changes in [Ca2+]i and tension during phasic contractions were indistinguishable in myometrium taken before or after the onset of labor, enabling samples to be pooled. Oxytocin (10 nM) had no effect on basal [Ca2+]i or tension, but it increased both the [Ca2+]i and the tension recorded during phasic contractions. Analysis of the [Ca2+]i-tension relationship revealed that during the falling (relaxation) phase of the contractile response, oxytocin increased the tension recorded at each [Ca2+]i. By manipulating extracellular Ca2+ during phasic contractions, it was possible to ensure that the [Ca2+]i signals were similar in the presence and absence of oxytocin, yet oxytocin still improved the [Ca2+]i-tension relationship. We conclude that 10 nM oxytocin increases the [Ca2+]i sensitivity of the contractile proteins only after a contraction has begun, possibly by causing inhibition of myosin light chain phosphatase.
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PMID:Oxytocin increases the [Ca2+]i sensitivity of human myometrium during the falling phase of phasic contractions. 995 Jul 95


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