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Myometrial interstitial cells and the coordination of myometrial contractility.

Hutchings G, Williams O, Cretoiu D, Ciontea SM - J. Cell. Mol. Med. (2009)

Bottom Line: The dominant cell population of the uterine wall consists of smooth muscle cells that contain the contractile apparatus responsible for the generation of contractile force.Recent interest has focused on a new population of cells located throughout the myometrium on the borders of smooth muscle bundles.Calcium imaging of live tissue slices suggests that contractile signalling starts on the borders of smooth muscle bundles where m-ICLC are located and recently the possible role of extracellular ATP signalling from m-ICLC has been studied.

View Article: PubMed Central - PubMed

Affiliation: Perinatal Research Group, 10 floor, St Luc University Hospital, Brussels, Belgium. Graham.Hutchings@uclouvain.be

ABSTRACT
A strict regulation of contractility in the uterus and fallopian tube is essential for various reproductive functions. The uterus contributes, through either increased contractility or periods of relative quiescence, to: (i) expulsion of menstrual debris, (ii) sperm transport, (iii) adequate embryo placement during implantation, (iv) enlarging its capacity during pregnancy and (v) parturition. The dominant cell population of the uterine wall consists of smooth muscle cells that contain the contractile apparatus responsible for the generation of contractile force. Recent interest has focused on a new population of cells located throughout the myometrium on the borders of smooth muscle bundles. These cells are similar to interstitial cells of Cajal (ICC) in the gut that are responsible for the generation of electrical slow waves that control peristalsis. A precise role for myometrial Cajal-like interstitial cells (m-ICLC) has not been identified. m-ICLC express the c-kit receptor, involved in creating and maintaining the ICC phenotype in the gastrointestinal tract. However, both acute and prolonged inhibition of this receptor with the c-kit antagonist imatinib mesylate does not appear to affect the spontaneous contractility of myometrium. Calcium imaging of live tissue slices suggests that contractile signalling starts on the borders of smooth muscle bundles where m-ICLC are located and recently the possible role of extracellular ATP signalling from m-ICLC has been studied. This manuscript reviews the evidence regarding tissue-level signalling in the myometrium with a particular emphasis on the anatomical and possible functional aspects of m-ICLC as new elements of the contractile mechanisms in the uterus.

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Representative traces of myometrial human smooth muscle inhibition by imatinib 20 μM. Reprinted from Ref. [78], with permission from Elsevier.
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fig09: Representative traces of myometrial human smooth muscle inhibition by imatinib 20 μM. Reprinted from Ref. [78], with permission from Elsevier.

Mentions: Two observations are evident from the results of these experiments. First, the doses of imatinib that were used are very high compared with either the IC50 concentrations (between 0.1 and 1 μM) or the serum levels achieved in humans receiving the drug (approximately 4 μM for peak levels and 2 μM for trough values [74]). This raises the possibility that any effect seen with these high doses could be as a result of non-specific effects rather than as a consequence of c-kit inhibition. Secondly, the results from the different studies fall into two broad groups. Either only amplitude is decreased at high doses of imatinib or imatinib has effects on both frequency and amplitude and leads to the eventual abolition of contractions. Perhaps these differences could be explained by differences in species or tissue type, but regarding the two human myometrial studies, there are no obvious differences in methodology that could account for the conflicting results. Popescu’s team used non-pregnant myometrium (Fig. 9), but why this differs from pregnant myometrium is not easy to explain.


Myometrial interstitial cells and the coordination of myometrial contractility.

Hutchings G, Williams O, Cretoiu D, Ciontea SM - J. Cell. Mol. Med. (2009)

Representative traces of myometrial human smooth muscle inhibition by imatinib 20 μM. Reprinted from Ref. [78], with permission from Elsevier.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4496132&req=5

fig09: Representative traces of myometrial human smooth muscle inhibition by imatinib 20 μM. Reprinted from Ref. [78], with permission from Elsevier.
Mentions: Two observations are evident from the results of these experiments. First, the doses of imatinib that were used are very high compared with either the IC50 concentrations (between 0.1 and 1 μM) or the serum levels achieved in humans receiving the drug (approximately 4 μM for peak levels and 2 μM for trough values [74]). This raises the possibility that any effect seen with these high doses could be as a result of non-specific effects rather than as a consequence of c-kit inhibition. Secondly, the results from the different studies fall into two broad groups. Either only amplitude is decreased at high doses of imatinib or imatinib has effects on both frequency and amplitude and leads to the eventual abolition of contractions. Perhaps these differences could be explained by differences in species or tissue type, but regarding the two human myometrial studies, there are no obvious differences in methodology that could account for the conflicting results. Popescu’s team used non-pregnant myometrium (Fig. 9), but why this differs from pregnant myometrium is not easy to explain.

Bottom Line: The dominant cell population of the uterine wall consists of smooth muscle cells that contain the contractile apparatus responsible for the generation of contractile force.Recent interest has focused on a new population of cells located throughout the myometrium on the borders of smooth muscle bundles.Calcium imaging of live tissue slices suggests that contractile signalling starts on the borders of smooth muscle bundles where m-ICLC are located and recently the possible role of extracellular ATP signalling from m-ICLC has been studied.

View Article: PubMed Central - PubMed

Affiliation: Perinatal Research Group, 10 floor, St Luc University Hospital, Brussels, Belgium. Graham.Hutchings@uclouvain.be

ABSTRACT
A strict regulation of contractility in the uterus and fallopian tube is essential for various reproductive functions. The uterus contributes, through either increased contractility or periods of relative quiescence, to: (i) expulsion of menstrual debris, (ii) sperm transport, (iii) adequate embryo placement during implantation, (iv) enlarging its capacity during pregnancy and (v) parturition. The dominant cell population of the uterine wall consists of smooth muscle cells that contain the contractile apparatus responsible for the generation of contractile force. Recent interest has focused on a new population of cells located throughout the myometrium on the borders of smooth muscle bundles. These cells are similar to interstitial cells of Cajal (ICC) in the gut that are responsible for the generation of electrical slow waves that control peristalsis. A precise role for myometrial Cajal-like interstitial cells (m-ICLC) has not been identified. m-ICLC express the c-kit receptor, involved in creating and maintaining the ICC phenotype in the gastrointestinal tract. However, both acute and prolonged inhibition of this receptor with the c-kit antagonist imatinib mesylate does not appear to affect the spontaneous contractility of myometrium. Calcium imaging of live tissue slices suggests that contractile signalling starts on the borders of smooth muscle bundles where m-ICLC are located and recently the possible role of extracellular ATP signalling from m-ICLC has been studied. This manuscript reviews the evidence regarding tissue-level signalling in the myometrium with a particular emphasis on the anatomical and possible functional aspects of m-ICLC as new elements of the contractile mechanisms in the uterus.

Show MeSH