Myometrial

Barusiban is a long-acting, selective antagonist of OTR that is in development for preterm labour. It has a 300-fold higher affinity for the OTR than for the Vi AR and hence more selective action than atosiban on myometrial tissues. The duration of action may be longer then that of atosiban, providing the convenience... 

Weiner CP, Mason CW, Buhimschi C, Hall G, Swaan PW, Buhimschi I. Changes in uterine GTPase activity are not consistent with changes in expression of Ga subunits of heterotrimeric G-proteins A potential mechanism for myometrial quiescence. Society of Gynecological Investigation. Los Angeles, CA, 2005. 

Lipton A, Vinijsanun A, Martin L (1984) Acute inhibition of rat myometrial responses to oxytocin by tamoxifen stereoisomers and oestradiol. J Endocrinol 103(3) 383-388... 

Black et al. (1994) first reported that raloxifene was effective in terms of bone loss prevention and lipid pattern without any stimulatory effect on the uterus. Specifically, the histological examination of uteri from ovariectomized rats treated with raloxifene alone shows poor effects on myometrial thickness and a uterine weight slightly higher than untreated ovariectomized rats (Black et al. 1994). 

FIG. 5. Simultaneous and reproducible measurements of changes in SR and cytosolic Ca2+ in response to agonists. Pregnant rat myometrial cells were superfused with Krebs (2 mM Ca2+) and Carbachol (in Ca-free solution) applied as indicated. Repetitive applications of Carbachol evoked reproducible [Ca2+]j elevations (bottom trace) and SR [Ca2+]L decreases (upper traces). Left-hand axis cytosolic Ca2+. Right-hand axis intraluminal (SR) Ca2+changes, measured with mag-fluo-4. (Taken from Shmigol et al 2001.)... 

Arnaudeau S, Lepretre N, Mironneau J 1994a Oxytocin mobilizes calcium from a unique heparin-sensitive and thapsigargin-sensitive store in single myometrial cells from pregnant rats. Pflugers Arch 428 51—59... 

Arnaudeau S, Lepretre N, Mironneau J 1994b Chloride and monovalent ion-selective cation currents activated by oxytocin in pregnant rat myometrial cells. Am J Obstet Gynecol 171 491-501... 

Inoue Y, Sperelakis N 1991 Gestational change in Na+ and Ca2+ channel current densities in rat myometrial smooth muscle cells. Am J Physiol 260 C658-C663 Kamishima T, McCarron JG 1996 Depolarization-evoked increases in cytosolic calcium concentration in isolated smooth muscle cells in rat portal vein. J Physiol 492 61-74 Khan R, Mathroo-Ball B, Arulkumaran S, Ashford ML 2001 Potassium channels in the human myometrium. Exp Physiol 86 255-264... 

Martin C, Hyvelin JM, Chapman KE, Marthan R, Ashley RH, Savineau JP 1999 Pregnant rat myometrial cells show heterogeneous ryanodine- and caffeine-sensitive calcium stores. Am J Physiol 277 C243-C252... 

Young We have data showing that induction of a Ca2+ wave in cultured myometrial cells that lack L-type Ca2+ channels causes activation of Ca2+-activated K+ channels that we think are store-operated. This is just with passage of a Ca2+ wave without thapsigargin. 

Sarcoplasmic reticulum, calcium waves and myometrial signalling... 

Clapham DE, Lechleiter JD, Girard S 1993 Intracellular waves observed by confocal microscopy from Xenopus oocytes. Adv Second Messenger Phosphoprot Res 28 161-165 Martin C, Chapman KE, Thornton S, Ashley RH 1999 Changes in the expression of myometrial ryanodine receptor mRNAs during human pregnancy. Biochim Biophys Acta 1451 343—352 McLean M, Smith R 2001 Corticotrophin-releasing hormone and human parturition. Reproduction 121 493-501... 

Morgan JM, De Smedt H, Gillespie JI1996 Identification of three isoforms of the InsP3 receptor in human myometrial smooth muscle. Pfliiger s Arch 431 697—705... 

Yamamoto T [1995] Effects of estrogens on Ca2+ channels in myometrial cells isolated from pregnant rats. Am J Physiol 268 C64-C69... 

Myometrial stimulants. The neurohypophyseal hormone oxytocin (p. 242) is given parenterally (or by the nasal or buccal route) before, during, or after labor in order to prompt uterine contractions or to enhance them. Certain prostaglandins or analogues of them (p. 

Release of oxytocin at this stage of parturition promotes prostaglandin production, particularly of the E and F series, within the decidua these prostaglandins are powerful myometrial stimulants and thus further enhance uterine contractions. The prostaglandin concentration in maternal serum and amniotic fluid increases with the progression of labor. 

Uterine relaxation is mediated in part through inhibition of MLCK. This inhibition results from the phosphorylation of MLCK that follows the stimulation of myometrial (3-adrenoceptors relaxation involves the activity of a cyclic adenosine monophosphate (cAMP) mediated protein kinase, accumulation of Ca++ in the sarcoplasmic reticulum, and a decrease in cytoplasmic Ca. Other circulating substances that favor quiescence of uterine smooth muscle include progesterone, which increases throughout pregnancy, and possibly prostacyclin. Progesterone s action probably involves hyperpolarization of the muscle cell membrane, reduction of impulse conduction in muscle cells, and increased calcium binding to the sarcoplasmic reticulum. 

Oxytocin (Pitocin, Syntocinon) is a cyclic 8-amino acid peptide that is synthesized in the paraventricular nucleus of the hypothalamus and transported within hypothalamic neurons (in association with neurophysin) to the posterior pituitary for storage. Its mechanism of action involves the direct stimulation of oxytocin receptors found on the myometrial cells. Oxytocin circulates unbound in the plasma, where it has a half-Ufe of approximately 15 minutes. It is primarily inactivated in the kidneys and liver. 

---