Oxytocin Receptors and Parturition. I. Control of Oxytocin Receptor Concentration in the Rat Myometrium at Term*

Alexandrová, M; Soloff, Melvyn S.

doi:10.1210/endo-106-3-730

Cited by 202 publications

(76 citation statements)

References 40 publications

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“…In pregnant mammals including humans, an abrupt increase in oxytocin binding sites in the uterus may occur at approximately 24 h before the onset of labor, reaching the greatest levels during labor and sharply decreasing after parturition to reach baseline levels 2-5 days postpartum (Alexandrova and Soloff, 1980;Fuchs et al, 1984;Soloff, 1990). An increase in myometrial sensitivity to oxytocin and plasma oxytocin levels was observed to occur simultaneously to the increase in the number of oxytocin receptors (Soloff, 1990).…”

Section: Discussionmentioning

confidence: 99%

Influence of time at which oxytocin is administered during labor on uterine activity and perinatal death in pigs

et al. 2007

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Oxytocin is extensively used to induce or augment uterine contractions, especially to facilitate the third stage of labor in humans. Administration of oxytocin to parturient sows reduces duration of labor whereas mortality of the offspring may remain unchanged. This study aimed to evaluate whether time of administration of oxytocin during parturition may alter the uterine response and fetal outcomes. Two hundred parturient sows were randomly assigned to intramuscularly receive either saline solution (control group) or oxytocin 0.083 IU/kg immediately after the delivery of the 1 st , 4 th or 8 th piglet (groups O-1, O-4 and O-8, respectively). Uterine effects and fetal outcomes were registered in all groups. The duration of labor was 20-40 min shorter (P < 0.0001) and time interval between babies was reduced by 3-5 min (P < 0.0001) in the three groups receiving oxytocin. The duration and intensity of contractions, meconium-stained piglets and intrapartum deaths decreased as time at which oxytocin administered during labor was increased. In group O-8, we observed approximately 70% less meconium-stained piglets and intrapartum deaths than in the control group. In conclusion, oxytocin administered at early phases of parturition to sows may increase duration and intensity of uterine contractions as well as adverse fetal outcomes.

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Section: Discussionmentioning

confidence: 99%

Influence of time at which oxytocin is administered during labor on uterine activity and perinatal death in pigs

et al. 2007

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“…In our experiments the maximal binding capacity for [3H]oxytocin in this species was severalfold higher as compared to a uterine membrane preparation from either rat or rabbit at late pregnancy. Even at early term the concentration of oxytocin receptors in rat and rabbit is lower [4,18] as compared to the guinea By using a series of selective oxytocin agonists with either sarcosine or N-methylalanine in position 7 of oxytocin it could be demonstrated that this receptor has the expected ligand specificity of an oxytocin receptor. The guinea pig receptor shows a ligand specificity similar to that of the rat uterine receptor; however, the receptor affinity of N-methylalanine analogues is higher in guinea pig than in rat [19].…”

Section: Discussionmentioning

confidence: 99%

Identification of a myometrial oxytocin‐receptor protein

Fahrenholz

Hackenberg

Muller

1988

European Journal of Biochemistry

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The specific binding of [3H]oxytoxin to uterine membrane peparations derived from different species at late pregnancy was examined. The highest receptor density (b,,, value) was found in membranes derived from the myometria of guinea pigs between day 60 post-conception (b,,, = 3.6 f 0.1 pmol/mg) and day 65 (b,,, = 4.4 f 0.1 pmol/mg). The similarity of & values for oxytocin binding (Kd = 2.6 f 0.2 nM) and for vasopressin binding (& = 2.1 f 0.4 nM) to the same membranes derived from a guinea pig myometrium indicate a homogenous population of high-affinity binding sites which do not discriminate between these two hormones.Competitive binding experiments with specific oxytocin agonists containing either sarcosine or N-methylalanine in the place of Pro' demonstrated that these myometrial receptors have the pharmacological properties of oxytocin receptors.The analogue of 1 -deamino-[8-lysine]vasopressin containing a photoreactive azidophenylamidino group at the sidechain of Lys' retained roughly the same receptor affinity as oxytocin. In photoaffinity labelling experiments with the tritium-labelled analogue a membrane protein from guinea pig myometrium with an apparent relative molecular mass M , of 78000 f 5000 (n = 13) was preferentially labelled. The labelling of this protein was completely suppressed by a 100-fold molar excess of either oxytocin, or [Sar7]oxytocin or [Thr4, Sar7]oxytocin, but not by other peptide hormones. These results provide evidence that the labelled 78000-M, protein is a myometrial oxytocin-receptor protein.The neurohypophysial nonapeptide oxytocin stimulates the contraction of smooth muscle cells in the myometrial layer of the uterus. The existence of specific oxytocin receptors has been demonstrated in the animal and human myometrium [l, 21. The oxytocin sensitivity of the uterus increases during pregnancy and is accompanied by an estrogen-induced increase in the concentration of myometrial oxytocin receptors at late pregnancy and at early-term labor [3 -51.The molecular events which are triggered after binding of oxytocin to its myometrial receptor are not well understood. There is evidence for inositol phosphate production [6] and for Ca2+ influx in the myometrium [7]. Furthermore, oxytocin has been shown to inhibit a (CaZ+ + MgZ+) ATPase [8] and to increase the intercellular communication via gap junctions [9].Little is known about the oxytocin receptor's physical properties. Soloff and Fernstrom were able to solubilize with a relatively low yield (20 -25%) oxytocin binding sites from the pregnant rat myometrium and the rat mammary gland with a zwitterionic detergent [lo]. Gel filtration analysis indicated that the solubilized oxytocin binding components from rat mammary gland were present in multiple molecular mass forms: M, values ranged from 40000 to greater than 200000. The uterine oxytocin-receptor protein, however, has not yet been identified. The present study was performed to identify myometrial oxytocin-receptor proteins. For this purpose, a myometrial membrane from guinea pig c...

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“…synthesis of an inhibitory substance in response to oestrogen and for the periods of enhanced activity, e.g. prostaglandin (PG) secretion, or increased population of oxytocin receptors (Alexandrova & Soloff, 1980), it is very difficult to postulate a mechanism which would account for the alternation of these two states. Unpublished experiments (Lye, 1980) in which oestrogen-treated ewes were infused with the PG synthetase inhibitor, meclofenamic acid, suggested that this oestrogen-induced pattern of activity was prostaglandin-dependent, since both the high-activity and quiescent periods were abolished by this drug.…”

Section: Discussionmentioning

confidence: 99%