Mechanisms of Direct Inhibitory Action of Propofol on Uterine Smooth Muscle Contraction in Pregnant Rats

2001 ◽  
Vol 95 (5) ◽  
pp. 1245-1255 ◽  
Author(s):  
Naoki Tsujiguchi ◽  
Michiaki Yamakage ◽  
Akiyoshi Namiki
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Receptor Binding ◽  
Muscle Tension ◽  
Smooth Muscle Contraction ◽  
Inhibitory Effect ◽  
Late Gestation ◽  
Dependent Manner ◽  
Pregnant Rats ◽  
Uterine Smooth Muscle

Background Although propofol directly inhibits uterine smooth muscle contraction, the mechanisms of this effect are still unknown. The current study aimed to clarify the mechanisms of the inhibitory effect of propofol on oxytocin-induced uterine smooth muscle contraction by measuring (1) the concentration of intracellular free Ca(2+) ([Ca(2+)](i)) simultaneously with muscle tension, (2) the amount of intracellular inositol 1,4,5-triphosphate ([IP(3)](i)), and (3) voltage-dependent Ca(2+) channel (VDCC) activity. Methods Uterine smooth muscle tissues were obtained from pregnant rats (in late gestation). [Ca(2+)](i) with isometric tension was monitored by the 500-nm light emission ratio of preloaded Ca(2+) indicator fura-2. [IP(3)](i) and VDCC activity were measured by radioimmunoassay and patch clamp techniques, respectively. The uterine smooth muscle was stimulated by 20 nm oxytocin and exposed to propofol (10(-7) approximately 10(-4) m). Results Propofol had significant inhibitory effects on oxytocin-induced uterine smooth muscle contraction and increased [Ca(2+)](i) in pregnant rats in a dose-dependent manner, without affecting the agonist-receptor binding affinity. Propofol inhibited the increase in [IP(3)](i) induced by oxytocin. Propofol also inhibited VDCC activity in both activated and inactivated states. The solvent Intralipid had no effects on these parameters. Conclusions Propofol inhibits oxytocin-induced uterine smooth muscle contraction, at least in part, by decreasing [Ca(2+)](i) without affecting agonist-receptor binding; the inhibitory effect of propofol on [Ca(2+)](i) might be mediated both by a decrease in [IP(3)](i) and by inhibition of VDCC activity.

Effect of Volatile Anesthetics with and without Verapamil on Intracellular Activity in Vascular Smooth Muscle

1996 ◽  
Vol 84 (6) ◽  
pp. 1465-1474 ◽  
Author(s):  
Hitoshi Namba ◽  
Hideaki Tsuchida
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Muscle Tension ◽  
Volatile Anesthetics ◽  
Smooth Muscle Contraction ◽  
Isometric Tension ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Pharmacomechanical Coupling ◽  
Intracellular Action

Background Although halothane and isoflurane inhibit receptor agonist-induced smooth muscle contraction by inhibiting Ca2+ influx via the L-type voltage-dependent Ca2+ channels, their effects on pharmacomechanical coupling remained to be clarified. The intracellular action of both anesthetics was studied during agonist-induced contractions using the Ca2+ channel blocker verapamil. Methods Isolated spiral strips of rat thoracic aorta with endothelium removed were suspended for isometric tension recordings in physiologic salt solution. Cytosolic concentration of Ca2+ ([Ca2+]i) was measured concomitantly using fura-2-Ca2+ fluorescence. Muscle contraction was evoked by the receptor agonists with 30 nm norepinephrine or 10 microM prostaglandin F2 alpha (PGF2 alpha), followed by exposure to halothane, at 0%, 1%, 2%, and 3% or isoflurane, at 2% and 4%. The effects of the anesthetics were compared with those of 0.1-1 microM verapamil (n = 8 for each condition). To clarify the intracellular action of the volatile anesthetics on agonist-induced contractions, this procedure was repeated for the anesthetics only in the presence of 1 microM verapamil (n = 8 for each condition). The effects of both anesthetics were also examined in nonreceptor-mediated contractions evoked with a 1-microM dose of the protein kinase C activator, 12-deoxyphorbol 13-isobutylate, which increases the Ca2+ sensitivity of the contractile elements (n = 8 for each). Results Halothane, isoflurane, and verapamil suppressed norepinephrine-and PGF2 alpha-induced increases in muscle tension and [Ca2+]i in a concentration-dependent manner. The Ca2+-tension regression lines suggested that the volatile anesthetics reduced Ca2+ sensitivity of the contractile elements during PGF2 alpha-induced contraction. Pretreatment of the muscle strip with verapamil revealed that halothane and isoflurane released Ca2+ during norepinephrine-induced contraction and that [Ca2+]i-tension relationship was modulated during PGF2 alpha-induced contractions. Halothane at 2% and 3% and isoflurane at 4% suppressed 12-deoxyphorbol 13-isobutylate-induced increases in muscle tension, whereas they enhanced increases in [Ca2+]i, indicating that both anesthetics suppressed Ca2+ sensitivity during 12-deoxyphorbol 13-isobutylate-induced contraction. Conclusions Verapamil pretreatment unmasked the intracellular action of the anesthetics. Halothane and isoflurane influenced pharmacomechanical coupling during agonist-induced contraction.

Tianeptine’s effects on spontaneous and Ca2+-induced uterine smooth muscle contraction

2012 ◽  
Vol 99 (2) ◽  
pp. 140-147
Author(s):  
Zorana Oreščanin-Dušić ◽  
Č. Miljević ◽  
M. Slavić ◽  
A. Nikolić-Kokić ◽  
D. Blagojević ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Smooth Muscle Contraction ◽  
Uterine Smooth Muscle

scholarly journals Class II PI3Ks α and β Are Required for Rho-Dependent Uterine Smooth Muscle Contraction and Parturition in Mice

Endocrinology ◽  
2018 ◽  
Vol 160 (1) ◽  
pp. 235-248 ◽  
Author(s):  
Md Azadul Kabir Sarker ◽  
Sho Aki ◽  
Kazuaki Yoshioka ◽  
Kouji Kuno ◽  
Yasuo Okamoto ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Class Ii ◽  
Smooth Muscle Contraction ◽  
Uterine Smooth Muscle

Inhibitory effect of interleukin-6 on vascular smooth muscle contraction

1994 ◽  
Vol 266 (3) ◽  
pp. H898-H902 ◽  
Author(s):  
F. Ohkawa ◽  
U. Ikeda ◽  
K. Kawasaki ◽  
E. Kusano ◽  
M. Igarashi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Contraction ◽  
Interleukin 6 ◽  
Smooth Muscle Contraction ◽  
Inhibitory Effect ◽  
Sprague Dawley ◽  
Intracellular Cgmp ◽  
Dependent Relationship ◽  
Vascular Smooth Muscle Contraction

Our objective was to investigate the direct effect of interleukin-6 (IL-6) on the vascular smooth muscle contraction. We measured the contraction of endothelium-denuded aortic rings isolated from Sprague-Dawley rats. We also investigated the involvement of vasodilator prostaglandin and guanosine 3',5'-cyclic monophosphate (cGMP) productions in the effect of IL-6 using cultured rat vascular smooth muscle cells (VSMC). Exposing the aortic rings to recombinant murine IL-6 (50 U/ml) for 180 min significantly suppressed the phenylephrine (10(-9)-10(-5) M)-induced contraction. This inhibitory effect of IL-6 on the contraction tended to exhibit a dose-dependent relationship (0.5-50 U/ml). The effect of IL-6 was totally eliminated in the presence of indomethacin (10(-5) M). The release of immunoreactive 6-ketoprostaglandin F1 alpha from cultured rat VSMC was significantly increased by exposure to IL-6. Intracellular cGMP concentration in VSMC was not affected by IL-6. In conclusion, IL-6 is a potent inhibitor of the alpha-adrenergic-stimulated contraction of vascular smooth muscle. Its action is endothelium independent and mediated by the increased synthesis of prostacyclin in VSMC.

Norepinephrine and endothelin activate diacylglycerol kinases in caveolae/rafts of rat mesenteric arteries: agonist-specific role of PI3-kinase

2007 ◽  
Vol 292 (5) ◽  
pp. H2248-H2256 ◽  
Author(s):  
Christopher J. Clarke ◽  
Vasken Ohanian ◽  
Jacqueline Ohanian
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Contraction ◽  
Smooth Muscle Contraction ◽  
Pi3 Kinase ◽  
Mesenteric Arteries ◽  
Dependent Manner ◽  
Kinase Inhibition ◽  
Small Arteries ◽  
Vascular Smooth Muscle Contraction

The phosphatidylinositol (PI) signaling pathway mediates norepinephrine (NE)- and endothelin-1 (ET-1)-stimulated vascular smooth muscle contraction through an inositol-trisphosphate-induced rise in intracellular calcium and diacylglycerol (DG) activation of protein kinase C (PKC). Subsequent activation of DG kinases (DGKs) metabolizes DG to phosphatidic acid (PA), potentially regulating PKC activity. Because precise regulation and spatial restriction of the PI pathway is necessary for specificity, we have investigated whether this occurs within caveolae/rafts, specialized plasma membrane microdomains implicated in vascular smooth muscle contraction. We show that components of the PI signaling cascade-phosphatidylinositol 4,5-bisphosphate (PIP2), PA, and DGK-θ are present in caveolae/rafts prepared from rat mesenteric small arteries. Stimulation with NE or ET-1 induced [33P]PIP2 hydrolysis solely within caveolae/rafts. NE stimulated an increase in DGK activity in caveolae/rafts alone, whereas ET-1 activated DGK in caveolae/rafts and noncaveolae/rafts; however, [33P]PA increased in all fractions with both agonists. Previously, we reported that NE activated DGK-θ in a phosphatidylinositol 3-kinase (PI3-kinase)-dependent manner; here, we describe PI3-kinase-dependent DGK activation and [33P]PA production in caveolae/rafts in response to NE but not ET-1. Additionally, PKB, a potential activator of DGK-θ, translocated to caveolae/rafts in response to NE but not ET-1, and PI3-kinase inhibition prevented this. Furthermore, PI3-kinase inhibition reduced the sensitivity of contraction to NE but not ET-1. Our study shows that caveolae/rafts are major sites of vasoconstrictor hormone activation of the PI pathway in intact small arteries and suggest a link between lipid signaling events within caveolae/rafts and contraction.

scholarly journals Effects of fetal hypothyroidism on uterine smooth muscle contraction and structure of offspring rats

2018 ◽  
Vol 103 (5) ◽  
pp. 683-692 ◽  
Author(s):  
Fatemeh Bagheripuor ◽  
Mahboubeh Ghanbari ◽  
Abbas Piryaei ◽  
Asghar Ghasemi
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Smooth Muscle Contraction ◽  
Uterine Smooth Muscle ◽  
Fetal Hypothyroidism

scholarly journals Effects of enantiomers of β2-agonists on ACh release and smooth muscle contraction in the trachea

1998 ◽  
Vol 274 (1) ◽  
pp. L32-L38 ◽  
Author(s):  
Xiang-Yang Zhang ◽  
Feng-Xia Zhu ◽  
Michal A. Olszewski ◽  
N. Edward Robinson
Keyword(s):  
Smooth Muscle ◽  
High Performance ◽  
Muscle Tension ◽  
Electrical Field Stimulation ◽  
Smooth Muscle Contraction ◽  
Acute Administration ◽  
Dependent Manner ◽  
Ach Release ◽  
Concentration Dependent Manner ◽  
Parasympathetic Nerves

The β2-agonists currently used as bronchodilators are racemic mixtures of R- and S-enantiomers. In the present study, we examined the effects of enantiomers of the β2-agonists albuterol and formoterol on acetylcholine (ACh) release from equine trachealis parasympathetic nerves. ACh release was evoked by electrical field stimulation (20 V, 0.5 ms, 0.5 Hz) and measured by high-performance liquid chromatography coupled with electrochemical detection. We also tested the effects of enantiomers of albuterol and formoterol on equine tracheal smooth muscle (TSM) contraction in response to exogenous ACh. R- and RS-albuterol (10−8 to 10−5 M) and RR- and RR/SS-formoterol (10−8 to 10−5 M) augmented ACh release in a concentration-dependent manner. Beginning at 10−6 M, SS-formoterol significantly increased ACh release, and at 10−5 M, release increased by 71.9 ± 8.7% over baseline. This effect was only observed, however, when the prejunctional muscarinic autoinhibitory effect of ACh was prevented with atropine. Both the RR- and SS-formoterol-induced increases in ACh release were abolished by the β2-antagonist ICI-118551 (3 × 10−7 M). The effect of S-albuterol on ACh release was variable, and the mean increase induced by 10−5 M was 30.8 ± 16.1% in the presence of atropine. In the muscle tension study, R- and RS-albuterol and RR- and RR/SS-formoterol (10−8 to 10−5 M) but not the S-enantiomers inhibited TSM contraction. Even though R-enantiomers augment ACh release, they potently inhibit TSM contraction. Because racemic β2-agonists are bronchodilators on acute administration, the postjunctional spasmolytic effects of R-enantiomers predominate over the spasmogenic effect evoked via increased ACh release. The S-enantiomers, in contrast, do not inhibit TSM contraction and therefore would not contribute to the observed bronchodilation of the racemate. The S-enantiomers do prejunctionally facilitate ACh release when prejunctional muscarinic autoreceptors are dysfunctional, suggesting a potentially deleterious effect.

Erratum to: Tianeptine’s effects on spontaneous and Ca2+-induced uterine smooth muscle contraction

2012 ◽  
Vol 99 (3) ◽  
pp. 364-364
Author(s):  
Z. Oreščanin-Dušić ◽  
Č. Miljević ◽  
M. Slavić ◽  
A. Nikolić-Kokić ◽  
R. Paskulin ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Smooth Muscle Contraction ◽  
Uterine Smooth Muscle

Role of Intracellular Ca2+Stores in the Inhibitory Effect of Halothane on Airway Smooth Muscle Contraction 

1998 ◽  
Vol 89 (1) ◽  
pp. 165-173 ◽  
Author(s):  
Michiaki Yamakage ◽  
Shinji Kohro ◽  
Takashi Matsuzaki ◽  
Hideaki Tsuchida ◽  
Akoyoshi Namiki
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Airway Smooth Muscle ◽  
Muscle Tension ◽  
Inhibitory Effect ◽  
Intracellular Concentration ◽  
Dependent Manner ◽  
Release Channel ◽  
Dose Dependent

Background Halothane directly inhibits contraction of airway smooth muscle, mainly by decreasing the intracellular concentration of free Ca2+ ([Ca2+]i). The role of intracellular Ca2+ stores, sarcoplasmic reticulum, is still unclear. We investigated the role of sarcoplasmic reticulum in the inhibitory effect of halothane on contraction of airway smooth muscle by measuring [Ca2+]i and intracellular concentration of inositol 1,4,5-triphosphate ([IP3]i), a second messenger for release of Ca2+ from sarcoplasmic reticulum. Methods [Ca2+]i was monitored by measuring the 500-nm light emission ratio (F340/F380) of a Ca2+ indicator fura-2 with isometric tension of canine tracheal smooth muscle strip. During Ca2+-free conditions, carbachol (10(-5) M) was introduced with pretreatment of halothane (0-3%). During Ca2+-free conditions, 20 mM caffeine, a Ca2+-induced Ca2+ release channel opener, was introduced with or without halothane. We measured [IP3]i during exposure to carbachol and halothane by radioimmunoassay technique. Results Pretreatment with halothane significantly diminished carbachol-induced increases in [Ca2+]i by 77% and muscle tension by 83% in a dose-dependent manner. Simultaneous administration of halothane significantly enhanced caffeine-induced transient increases in [Ca2+]i and muscle tension in a dose-dependent manner, by 97% and 69%, respectively. Pretreatment with halothane abolished these responses. Rapid increase in [IP3]i produced by carbachol was significantly inhibited by 32% by halothane in a dose-dependent manner. Conclusions Halothane, during Ca2+-free conditions, inhibits transient contraction of airway smooth muscle induced by muscarinic receptor stimulation, mainly by attenuating the increase in [Ca2+]i. Depletion of Ca2+ from sarcoplasmic reticulum via Ca2+-induced Ca2+ release channels also may contribute to the attenuation of the increase in [Ca2+]i by halothane.

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