Possible role of gap junctions in activation of myometrium during parturition

Garfield, Robert E.; Sims, Stephen M.; Kannan, Mathur; Daniel, E. E.

doi:10.1152/ajpcell.1978.235.5.c168

Cited by 167 publications

(66 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition the great variation of individual propagation-times that were measured both before and after delivery remains puzzling. Gap-junctions between myometrial cells probably underlie the myogenic propagation of electrical activity in the uterus and in the rat their formation seems to be essential in the process of initiation of parturition (Garfield et al, 1978). If the same is true in the sow, one must postulate an unequal distribution of fapjunctions between bundles of myometrial cells to explain the large differences in propagation-time of even two successive activity phases.…”

Section: Resultsmentioning

confidence: 99%

Myometrial activity and expulsion of fetuses

Taverne

Naaktgeboren

Weyden

1979

Animal Reproduction Science

View full text Add to dashboard Cite

Chronic implantation of extracellular electrodes on successive uterine segments of pregnant miniature sows and marking of their fetuses were performed in order to relate characteristics of uterine electrical activity during delivery with the sequence of expulsion of piglets.The electromyographs during parturition were characterized by synchronic and well propagated phases of activity that could first appear at any of the four electrodes; however, initiation occurred most frequently at the electrodes on the two extreme ends of a horn. Analysis of the relative occurrence of tubocervitally and cervicotubally propagated activity phases indicated that the latter were present, and even could dominate, before and during expulsion of the piglets. The mean duration of the activity phases decreased and their mean propagation-time along the horn increased after emptying of the horn. However, before as well as after completion of delivery, a wide range in propagation-time of even two successive activity phases was measured.It is concluded that a decrease in uterine volumeis responsible for the rather abrupt changes of the characteristics of myometrial activity upon delivery of the piglets from a horn. Possible explanations for the wide range of the propagation-times are discussed and it is suggested that the cervicotubally directed contractions prevents untimely interruption of the fetal-placentalmaternal connections of the piglets that are not yet due to be expelled.

show abstract

Section: Resultsmentioning

confidence: 99%

Myometrial activity and expulsion of fetuses

Taverne

Naaktgeboren

Weyden

1979

Animal Reproduction Science

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…Lindane inhibits gap junction communication between myometrial cells in culture and inhibits spontaneous oscillatory contractions of uterine strips in muscle baths, as shown previously Loch-Caruso, 1995, 1999; and confirmed in the present report. Based on the model of uterine contraction developed by Garfield and his colleagues (Garfield et al, 1978), it is suggested that lindane-induced inhibition of myometrial gap junction communication critically limits the intercellular transfer of signals necessary for coordination of oscillatory uterine contractions, and that, in the absence of transfer of these contractionregulating signals, oscillatory contractions cease.By demonstrating a concordance between effects of phospholipase pathway inhibitors on lindane-induced inhibition of myometrial gap junction communication and uterine contraction, the present study provides support for activation of phospholipase C as a mechanistic link between lindane's inhibitory actions on myometrial gap junctions and uterine contraction. The PI-PLC inhibitor ET-18-OCH 3 , but not the iPLA 2 inhibitor BEL or the PLD pathway interrupter ethanol, reversed lindane-induced inhibition of uterine contraction and inhibition of myometrial gap junction intercellular communication, consistent with a role for PLC in lindane's inhibitory actions on myometrial gap junction communication and contractions.…”

mentioning

confidence: 99%

Phospholipase-Mediated Inhibition of Spontaneous Oscillatory Uterine Contractions by Lindane in Vitro,

Wang

Loch‐Caruso

2002

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

Although regulation of uterine contractility is fundamental for parturition, mechanisms by which toxicants modify uterine muscle contractions remain poorly understood. In a previous cumulative concentration-response study, 10 μM lindane (γ-hexachlorocyclohexane) reduced contraction force and 30 μM lindane abolished contractions in Gestation Day 10 rat uterine strips when lindane was added to muscle baths at 10-min intervals. Other studies showed that brief (<10 min) exposures to 10-100 μM lindane inhibit gap junctions and activate phospholipase pathways in rat myometrial cells in culture. Consequently, lindane was used as a prototype toxicant with known uterine activity to investigate the hypothesis that activation of a specific phospholipase pathway provides a mechanistic link between inhibition of uterine contraction and inhibition of myometrial gap junctions. Uterine tissue and cells were pretreated with phospholipase pathway inhibitors to evaluate the role of phospholipase pathways in lindane's actions in the uterus. Concentrations of inhibitors were selected based on previous reports of effective concentrations for the enzyme activity and on pilot toxicity studies of the inhibitors on uterine contraction and gap junction communication. To monitor uterine contractions, longitudinal uterine strips were excised from Gestation Day 10 rats and suspended in isometric muscle baths, consistent with previous experiments. Exposure in vitro for 60 min to 10-50 μM lindane, an effective concentration range for the uterine responses of interest, revealed that 30 μM lindane rapidly abolished contractions. Subsequently, uterine strips were pretreated with phospholipase pathway inhibitors and then challenged with 30 μM lindane, the lindane concentration that elicited maximal inhibition of uterine contraction. Pretreatment with 20-50 μM of the phosphatidylinositol-specific phospholipase C inhibitor 1-O-octadecyl-2-O-methyl-sn -glycerol-3-phosphorylcholine (ET-18-OCH 3 ) reversed lindane-induced inhibition of spontaneous uterine contractions. Gap junction intercellular communication was monitored by injecting the fluorescent dye Lucifer yellow into rat myometrial cells grown in culture and assessing dye transfer to adjacent cells using epifluorescence microscopy. Similar to uterine contraction, pretreatment of cell cultures with phospholipase C inhibitors (30 μM ET-18-OCH 3 , 50 μM tricyclodecan-p-yl-xanthogenate · K [D609] or 50 μM tricyclodecan-p-yl-xanthogenate · K or 2-nitro-4-carboxyphenyl-N,Ndophenylcarbamate [NCDC]) partially reversed inhibition of dye transfer by 100 μM lindane, a 4To whom correspondence and reprint requests should be addressed at 1420 Washington Heights, Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109-2029. Fax: (734) lindane concentration previously shown to abolish myometrial Lucifer yellow dye transfer under similar culture conditions. In contrast, pretreatment with 20 μM of bromoenol lactone (BEL) to inhibit the calcium-i...

show abstract

“…Trosko et al (13) proposed a hypothesis that teratogenesis and tumor promotion may share for this idea is lent by teratology studies which found that exposure to EGME and EGEE significantly lengthened gestation in rats and mice (22,23). Since labor is dependent upon the formation of gap junctions between the myometrial cells (4), increased length of parturition might be a sign of gap junction interference. Other organ systems that rely on gap junctions such as the heart, intestines, and male reproductive system have also been adversely affected by some of these compounds (23).…”

Section: Discussionmentioning

confidence: 99%

“…Intercellular communication via gap junctions is a proposed mechanism for controlled transmission of in excitatory tissues such as the heart (3) and the myometrium during labor (4). Pools of small metabolites (1000 to 1500 daltons, depending upon configuration) are also shared among cells joined by gap junctions (2 This assay has been widely applied to identify tumor promoters (11,12) and was recently proposed as an assay for teratogens (13).…”

Section: Introductionmentioning

confidence: 99%

Interruption of cell-cell communication in Chinese hamster V79 cells by various alkyl glycol ethers: implications for teratogenicity.

Loch‐Caruso¹,

Trosko²,

Corcos³

1984

Environ Health Perspect

View full text Add to dashboard Cite

Intercellular communication most likely plays a significant coordinating role in morphogenesis. Blockage of a specific type of intercellular communication, that mediated by gap junctions, has been proposed as a mechanism of action of some teratogens. Several glycol ethers have recently been shown to be teratogenic in laboratory animals. Because these compounds are negative in genotoxic assays, it is suggested that they may act by nongenetic, perhaps membrane-mediated mechanisms.In the present study several structurally related alkyl glycol ethers were examined for their ability to block junction-mediated intercellular communication. Interruption of intercellular communication was measured in vitro by an assay that depends on the transfer of metabolites via gap junctions, i.e., metabolic cooperation. All compounds tested-ethylene glycol (EG), ethylene glycol monomethyl ether (EGME), ethylene glycol monoethyl ether (EGEE), ethylene glycol monopropyl ether (EGPE), and ethylene glycol monobutyl ether (EGBE)-were able to block metabolic cooperation in vitro. The potencies of the compounds were inversely related to the length of the aliphatic chain, the dose required for maximum blockage increasing as the aliphatic chain shortened. Some differences in the maximum amount of blockage were detected, but these were not consistent and hence were not considered significant. Cytotoxicity, as measured by cell survival, was also related to the structure of the compound, generally increasing with increased length of the aliphatic chain. There were structurally related differences in the concentration ranges over which the compounds were effective. The noncytotoxic ranges over which communication was blocked became reduced as the length of the aliphatic chain increased. EG was effective over the broadest range, followed by EGME. The remaining compounds had very narrow effective ranges relative to EG and EGME. Because they are effective over such broad noncytotoxic ranges, blockage of intercellular communication may be most significant as a teratogenic mechanism for EG and EGME. Although the other compounds in the series also blocked communication, they were more cytotoxic and they interrupted communication in a relatively narrow window of concentrations. Consequently, interrupted intercellular communication may be mixed with cytotoxicity in the embryo and the mother, and thus be less specific as a mechanism of teratogenesis for EGEE, EGPE and EGBE.

show abstract

Possible role of gap junctions in activation of myometrium during parturition

Cited by 167 publications

References 28 publications

Myometrial activity and expulsion of fetuses

Myometrial activity and expulsion of fetuses

Phospholipase-Mediated Inhibition of Spontaneous Oscillatory Uterine Contractions by Lindane in Vitro,

Interruption of cell-cell communication in Chinese hamster V79 cells by various alkyl glycol ethers: implications for teratogenicity.

Contact Info

Product

Resources

About