Human placental cholinergic system

Sastry, B. V. Rama; Olubadewo, Joseph O.; Harbison, Raymond D.; Schmidt, Dennis E.

doi:10.1016/0006-2952(76)90345-2

Cited by 134 publications

(21 citation statements)

References 22 publications

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“…Once acetylcholinesterase and pseudocholinesterases are inactivated, acetylcholine accumulates leading to cholinergic hyperactivity in tissues which express muscarinic and/or nicotinic receptors (for extensive review see Sastry 1997). Since the placenta has a functional cholinergic system complete with cholingeric receptors, choline acetyltransferase (ChAT) and cholinesterase, it is feasible that CPF imparts toxicity in the placenta by inducing cholinergic hyperactivity.…”

Section: Discussionmentioning

confidence: 99%

Characterization of chlorpyrifos-induced apoptosis in placental cells

Saulsbury¹,

Heyliger²,

Wang³

et al. 2008

Toxicology

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The mechanism by which chlorpyrifos exerts its toxicity in fetal and perinatal animals has yet to be elucidated. Since the placenta is responsible for transport of nutrients and is a major supplier hormones to the fetus, exposure to xenobiotics that alter the function or viability of placenta cells could ostensibly alter the development of the fetus. In this study, JAR cells were used to determine if CPF and the metabolites 3,5,6-trichloro-2-pyridinol (TCP) and chlorpyrifos-oxon (CPO) are toxic to the placenta. Our results indicate that chlorpyrifos (CPF), and its metabolite chlorpyrifos-oxon (CPO) caused a dose-dependent reduction in cellular viability with CPF being more toxic than its metabolites. Chlorpyrifos-induced toxicity was characterized by the loss of mitochondrial potential, the appearance of nuclear condensation and fragmentation, down-regulation of Bcl-2 as well as upregulation of TNFα and FAS mRNA. Pharmacological inhibition of FAS, nicotinic and TNF-α receptors did not attenuate CPF-induced toxicity. Atropine exhibited minimal ability to reverse toxicity. Furthermore, signal transduction inhibitors PD98059, SP600125, LY294002 and U0126 failed to attenuate toxicity; however, SB202190 (inhibitor of p38α and p38β MAPK) sensitized cells to CPF-induced toxicity. Pan-caspase inhibitor Q-VD-OPh produced a slight but significant reversal of CPF-induced toxicity indicating that the major caspase pathways are not integral to CPF-induced toxicity. Taken collectively, these results suggest that chlorpyrifos induces apoptosis in placental cells through pathways not dependent on FAS/TNF signaling, activation of caspases or inhibition of cholinesterase. In addition, our data further indicates that activation of p38 MAPK is integral to the protection cells against CPF-induced injury.

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Section: Discussionmentioning

confidence: 99%

Characterization of chlorpyrifos-induced apoptosis in placental cells

Saulsbury¹,

Heyliger²,

Wang³

et al. 2008

Toxicology

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“…ACh is expressed in the human placenta, where it acts via nAChR-mediated pathways to regulate nutrient transport, blood flow, and fluid volume in the placental vessels and vascularization during placental development (58). Immunohistochemical analyses revealed the expression of the α2, α3, α4, α5, α7, α9, and α10 subunits in different combinations in rat cytotrophoblasts, human and rat syncytiotrophoblasts, Hofbauer cells, human amniotic epithelium, and rat visceral yolk sac epithelium (59).…”

Section: -6-3 Placentamentioning

confidence: 99%

Basic and Clinical Aspects of Non-neuronal Acetylcholine: Overview of Non-neuronal Cholinergic Systems and Their Biological Significance

Kawashima¹,

2008

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Abstract. Acetylcholine (ACh) is a phylogenetically ancient molecule involved in cell-to-cell signaling in almost all life-forms on earth. Cholinergic components, including ACh, choline acetyltransferase, acetylcholinesterase, and muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively) have been identified in numerous non-neuronal cells and tissues, including keratinocytes, cancer cells, immune cells, urinary bladder, airway epithelial cells, vascular endothelial cells, and reproductive organs, among many others. Stimulation of the mAChRs and nAChRs elicits cell-specific functional and biochemical effects. These findings support the notion that non-neuronal cholinergic systems are expressed in certain cells and tissues and are involved in the regulation of their function and that cholinergic dysfunction is related to the pathophysiology of certain diseases. They also provide clues for development of drugs with novel mechanisms of action.

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“…It is present in the liver, intestinal mucosa, white matter of mammalian central nervous system and in higher levels in plasma 8 . Both CEs and BChE are expressed in human placenta 9,10 .…”

Section: Introductionmentioning

confidence: 99%