Supersensitivity to the stimulant action of noradrenaline on human myometrium near term

Pennefather, J.N.; Paull, John; Story, ME; Ziccone, SP

doi:10.1071/rd9930039

Cited by 9 publications

(7 citation statements)

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“…In contrast, the same study in the presence of WB4101 demonstrated an increased proportion (+ 63%) of the alB subtype in the high affinity agonist state. So, it is conceivable to assume that the atIB-subtype may account for the supersensitivity of the myometrium to the stimulating action of norepinephrine at the end of pregnancy in rats and humans [1,31]. This idea is also supported by the fact that the G-coupled state of aOB-adrenergic receptor is increased at term concomitantly with a norepinephrine release from the uterine sympathetic nerves [32] and a significant enhancement of Gatq subunit [24,33].…”

Section: Discussionmentioning

confidence: 94%

The Alpha1B-Adrenergic Receptor Subtype Activates the Phospholipase C Signaling Pathway in Rat Myometrium at Parturition1

Limon¹,

Mhaouty-Kodja²,

Coudouel³

et al. 1997

Biology of Reproduction

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This study demonstrates that alpha1-adrenergic receptors previously identified in the pregnant rat myometrium are heterogeneous. They can be subtyped alpha1A- and alpha1B-adrenergic receptors on the basis of their affinity for the antagonists WB4101 (alpha1A > alpha1B) and chloroethylclonidine (alpha1B selective). Between Day 21 of pregnancy and term, the proportion of [3H]prazosin binding sites with low affinity for WB4101 and sensitive to inactivation by 10(-5) M chloroethylclonidine under hypotonic conditions (alpha1B subtype) remained constant. In contrast, the number of [3H]prazosin binding sites with a high affinity for WB4101 and insensitive to chloroethylclonidine (alpha1A subtype) increased by 88% at term. The effect of 5'-guanylylimidodiphosphate (Gpp[NH]p) on competition of the agonist phenylephrine for [3H]prazosin binding in the presence of WB4101 or after chloroethylclonidine pretreatment indicates that the alpha1A-adrenergic receptor underwent uncoupling whereas the alpha1B-adrenergic receptor-G protein coupled state was increased (+ 63%). Phenylephrine consistently stimulated phospholipase C activity on membrane fractions prepared from term myometria. This stimulation was completely inhibited after 10(-5) M chloroethylclonidine but was not consistently decreased with 5-methylurapidyl, a selective alpha1A-antagonist. Furthermore QL antibody (anti-G alpha(q)/G alpha11) also specifically blocked the phenylephrine-stimulated phospholipase C activity. Altogether these results strongly suggest that activation of the alpha1B-adrenergic receptor subtype in the pregnant myometrium at term may contribute to the stimulation of the G alpha(q)/G alpha11/phospholipase C signaling pathway.

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Section: Discussionmentioning

confidence: 94%

The Alpha1B-Adrenergic Receptor Subtype Activates the Phospholipase C Signaling Pathway in Rat Myometrium at Parturition1

Limon¹,

Mhaouty-Kodja²,

Coudouel³

et al. 1997

Biology of Reproduction

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“…This could be the consequence of the decline in P concentration (Table 1) during the last days of pregnancy. Since it has been established that Gqa stimulates phosphoinositide-specific phospholipase C, its increment may account in part for the supersensitivity of the myometrium to the contractile effects of oxytocin [47] and norepinephrine [5,48] in relation with an increased number of oxytocin [41,49] and al-adrenergic receptors [50].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Myometrial Gi2, Gi3, and Gq Expression during Pregnancy. Effects of Progesterone and Estradiol1

Cohen‐Tannoudji

Mhaouty

Elwardy-Merezak

et al. 1995

Biology of Reproduction

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The possibility that progesterone or estradiol may regulate expression of G protein in the rat myometrium during the course of pregnancy has been investigated using 1) immunoblot analysis of Gi2 alpha, Gi3 alpha, and Gq alpha subunits and 2) hybridization blot analysis of subunit mRNA. Eighteen hours after administration, estradiol had significantly increased the levels of both Gi2 alpha subunit and Gi2 alpha mRNA (by 40% and 32%, respectively). In control pregnant rats, we observed similar changes at the end of pregnancy, when myometrial concentrations of estradiol had increased, i.e., a 41% increase in immunoreactive Gi2 alpha subunit that correlated with a parallel 45% increase in mRNA levels. In contrast, levels of immunoreactive Gi3 alpha subunit and mRNA, which decreased with advancing gestation, were not influenced by estradiol or progesterone administration. Progesterone administration resulted 30 h later in a significantly decreased level of Gq alpha immunoreactivity (32%) and Gq alpha mRNA (30%). In control rats, Gq alpha protein and mRNA were also significantly lower at midpregnancy under progesterone dominance vs. term. At this stage, a twofold increase in Gq alpha subunit correlated with a 40% increase in mRNA levels. These results demonstrate that myometrial Gi2 alpha and Gq alpha subunits are physiological targets for estradiol and progesterone, respectively, in vivo. Alterations of these G protein levels are discussed in relation to their mediating effects on adenylyl cyclase activity or the phospholipase C pathway during the course of pregnancy.

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“…In addition, progesterone has been shown to stabilize the high affinity state of the receptor, thus increasing the coupling of the 2 -ARs to adenylyl cyclase (Cohen-Tannoudji et al 1991) and facilitating uterine quiescence. In contrast, the 1 -ARs play an important role in the mechanism of parturition, as supported by several lines of evidence (Legrand & Maltier 1986, Pennefather et al 1993. At delivery, myometrial contractions are initiated primarily by a rise of intracellular Ca 2+ .…”

Section: Introductionmentioning

confidence: 94%

In vivo stimulation of the beta(2)-adrenergic pathway increases expression of the Gi proteins and the alpha(2)A-adrenergic receptor genes in the pregnant rat myometrium

Lecrivain

Mhaouty-Kodja²,

Cohen‐Tannoudji³

et al. 1998

Journal of Endocrinology

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Cross-regulations between G s and G i mediated pathways controlling the adenylyl cyclase activity have been clearly demonstrated in vitro. To elucidate whether activation of the -adrenergic pathway in the pregnant myometrium might affect G i proteins and 2 -adrenergic receptors (ARs), we treated late pregnant rats from day 18 to day 21 with twice-daily administration of isoproterenol (8 mg/ kg). This treatment increased myometrial cAMP levels and led after 76 h to a significant and maximal rise in the immunoreactive amount of myometrial G i 2 and G i 3 proteins (1·4-and 1·7-fold respectively) associated with a parallel increase of the steady-state levels of both G i 2 and G i 3 mRNA (1·6-and 1·9-fold respectively). Propranolol antagonized this response indicating the implication of the -adrenergic pathway. Nuclear run-on assays demonstrated that isoproterenol enhanced respectively by 1·3-and 1·2-fold the transcription rate of the G i 2 and G i 3 genes. Quantification of myometrial 2 -ARs by [3 H]rauwolscine binding revealed that the total number of receptors was also increased at 76 h by 1·7-fold when compared with controls, with no change in the affinity of the 2 -ARs for the ligand. This effect was antagonized by propranolol. Quantification of both 2A -and 2B -subtypes by Northern blotting analysis demonstrated that this elevation was due to a selective increase of the 2A -subtype mRNAs. The present results indicate that in vivo stimulation of the -adrenergic pathway by isoproterenol increases both G i 2 /G i 3 and 2A -AR expression in the pregnant rat myometrium. The possible contribution of such a mechanism in pregnancy-related changes of both entities is discussed.

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Supersensitivity to the stimulant action of noradrenaline on human myometrium near term

Cited by 9 publications

References 0 publications

The Alpha1B-Adrenergic Receptor Subtype Activates the Phospholipase C Signaling Pathway in Rat Myometrium at Parturition1

The Alpha1B-Adrenergic Receptor Subtype Activates the Phospholipase C Signaling Pathway in Rat Myometrium at Parturition1

Regulation of Myometrial Gi2, Gi3, and Gq Expression during Pregnancy. Effects of Progesterone and Estradiol1

In vivo stimulation of the beta(2)-adrenergic pathway increases expression of the Gi proteins and the alpha(2)A-adrenergic receptor genes in the pregnant rat myometrium

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