Human placental cholinergic system

Sastry, B. V. Rama

doi:10.1016/s0006-2952(97)00017-8

Cited by 104 publications

(39 citation statements)

References 53 publications

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“…Nicotine activates nicotine receptors in placenta and releases ACh [36]. Released ACh activates muscarinic receptors of endothelial cells and release endotheliumderived relaxing factor (EDRF) [32]. The increased peripheral vascular resistance produced by PGE 2 was antagonized by vascular dilation produced by EDRF/NO in the presence of nicotine in the present investigations.…”

Section: Discussionsupporting

confidence: 52%

“…Nicotine blocked the effects of PGE 2 completely. Human term placenta contains about 112 nmol/ ACh/g wet tissue, 7-fold higher than that of brain tissue [31,32]. ACh is released into both maternal and fetal circulations of term placenta [33][34][35].…”

Section: Discussionmentioning

confidence: 99%

“…Cotinine potentiates the effects of PGE 2 on placental vascular resistance which decreases fetal blood flow through the placenta. Decreased fetal placenta flow decreases the transport of amino acids and other nutrients from the maternal circulation into fetal circulation [32]. Cotinine acti-vates PLA 2 in very low concentrations and increases the production of PGE 2 .…”

Section: Discussionmentioning

confidence: 99%

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Prostaglandin E2 in Human Placenta: Its Vascular Effects and Activation of Prostaglandin E2 Formation by Nicotine and Cotinine

Sastry

Hemontolor²,

Olenick³

1999

Pharmacology

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Tobacco smoking by pregnant women increases the frequency of spontaneous abortions and preterm births. Human labor is associated with enhanced intrauterine phospholipid metabolism and production of prostaglandin E₂ (PGE₂) which induces labor, initiates uterine contractions and maintains the homeostasis of placental blood flow. Therefore, we studied: (a) the influence of nicotine and cotinine on the effects of PGE₂ on placental vasculature in perfused human placental cotyledon, and (b) the activation of placental phospholipase A₂ (PLA₂) by nicotine and cotinine using 1-palmitoyl-2-[1-¹⁴C]arachidonyl-phosphatidylethanolamine (PE, 2.2 nmol) as substrate. These studies revealed that: (1) increasing concentrations of PGE₂ (10– 150 ng/ml) increased umbilical perfusion pressure by 170 ± 10% (n = 6) of control (100%). Cotinine (2 µg/ml) enhanced this effect at all concentrations of PGE₂. Nicotine (2 µg/ml) prevented the effect of PGE₂; (2) both cotinine (EC₅₀ 470–500 fmol/l) and nicotine (EC₅₀ 18–32 pmol/l) activated PLA₂ in human placental tissues. These observations indicated that cotinine was more potent than in nicotine activating PLA₂ and potentiating the vasoconstrictive effects of PGE₂ on fetal placental circulation. Nicotine activates nicotinic receptors and releases placental acetylcholine, a vasodilator of placental arteries. Acetylcholine stimulates muscarinic receptors of endothelial cells resulting in the release of endothelium-derived relaxing factor (EDRF), and possibly nitric oxide. Therefore, nicotine prevents or abolishes the vasoconstrictive effects of PGE₂ through the release of EDRF. Cotinine is inactive at nicotinic and muscarinic receptors. Therefore, accumulation of cotinine, the major metabolite of nicotine, in fetal circulation may contribute to production of PGE₂ and induction of preterm labor and spontaneous abortions.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prostaglandin E2 in Human Placenta: Its Vascular Effects and Activation of Prostaglandin E2 Formation by Nicotine and Cotinine

Sastry

Hemontolor²,

Olenick³

1999

Pharmacology

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“…Like the bladder, the uterus is richly innervated by cholinergic neurons, and contractions are mainly mediated via M2 and M3 mAChR [149]. The human placenta is not cholinergically innervated; however, non-neuronal ACh is released via OCT1 and OCT3 [147] and can regulate different physiological functions like blood flow, vascularization and nutrient transport via nAChR [150]. Further, M1-M4 mAChR are expressed in the human placenta [151].…”

Section: Reproductive Systemmentioning

confidence: 99%

The Non-Neuronal Cholinergic System in Health and Disease

Beckmann¹,

Lips²

2013

Pharmacology

102

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Acetylcholine (ACh) is not only a neurotransmitter but is an ancient molecule that can be released by and act on non-neuronal cells. In these cells the system of ACh-synthesizing enzymes, transporters, receptors and degrading enzymes is termed the non-neuronal cholinergic system (NNCS). There is increasing evidence that the NNCS is dysregulated in various diseases and can have an influence on their pathology. However, for many organ systems not much is known about the expression and function of the NNCS. Thus, this review focusses on the role of the NNCS in different organ systems in health and disease. Dysregulation of ACh synthesis and release, mutations or polymorphisms in genes encoding NNCS components, and auto-antibodies against NNCS components are common factors influencing disease progression. Pharmacological agents targeting the NNCS are already successfully in clinical use for some disorders, indicating that interfering with this system is very promising and more research is needed to elucidate the role of the NNCS in different tissues and pathological states.

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“…Meanwhile it has been shown that the human placenta (chorionic plate, villus region, basal plate) expresses the complete cholinergic system, i.e. the synthesizing enzyme choline acetyltransferase, muscarinic and nicotinic receptors and the degrading enzyme cholinesterase (Sastry and Sadavongvivad 1979;Sastry 1997). Release of acetylcholine has been measured from isolated villus pieces or in vitro perfused placental cotyleda (Olubadewo and Sastry 1978;Boura et al 1986;Sastry 1997).…”

Section: Introductionmentioning

confidence: 99%

Release of non-neuronal acetylcholine from the human placenta: difference to neuronal acetylcholine

Wessler¹,

Róth²,

Schwarze³

et al. 2001

Naunyn-Schmiedeberg's Archives of Pharmacology

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The synthesis and release of non-neuronal acetylcholine, a widely expressed signaling molecule, were investigated in the human placenta. This tissue is free of cholinergic neurons, i.e. a contamination of neuronal acetylcholine can be excluded. The villus showed a choline acetyltransferase (ChAT) activity of 0.65 nmol/mg protein per h and contained 500 nmol acetylcholine/g dry weight. In the absence of cholinesterase inhibitors the release of acetylcholine from isolated villus pieces amounted to 1.3 nmol/g wet weight per 10 min corresponding to a fractional release rate of 0.13% per min. The following substances did not significantly modify the release of acetylcholine: oxotremorine (1 microM), scopolamine (1 microM), (+)-tubocurarine (30 microM), forskolin (30 microM), ouabain (10 microM), 4alpha-phorbol 12,13-didecanoate (1 microM) and tetrodotoxin (1 microM). Removal of extracellular calcium, phorbol 12,13-dibutyrate (1 microM) and colchicine (100 microM) reduced the acetylcholine release between 30% and 50%. High potassium chloride (54 mM and 108 mM) increased the acetylcholine release slightly (by about 30%). A concentration of 10 microM nicotine was ineffective, but 100 microM nicotine enhanced acetylcholine release gradually over a 50-min period without desensitization of the response. The facilitatory effect of nicotine was prevented by 30 microM (+)-tubocurarine. Inhibitors of cholinesterase (physostigmine, neostigmine; 3 microM) facilitated the efflux of acetylcholine about sixfold, and a combination of both (+)-tubocurarine (30 microM) and scopolamine (1 microM) halved the enhancing effect. In conclusion, release mechanisms differ between non-neuronal and neuronal acetylcholine. Facilitatory nicotine receptors are present which are activated by applied nicotine or by blocking cholinesterase. Thus, cholinesterase inhibitors increase assayed acetylcholine by two mechanisms, protection of hydrolysis and stimulation of facilitatory nicotine receptors.

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Human placental cholinergic system

Cited by 104 publications

References 53 publications

Prostaglandin E<sub>2</sub> in Human Placenta: Its Vascular Effects and Activation of Prostaglandin E<sub>2</sub> Formation by Nicotine and Cotinine

Prostaglandin E<sub>2</sub> in Human Placenta: Its Vascular Effects and Activation of Prostaglandin E<sub>2</sub> Formation by Nicotine and Cotinine

The Non-Neuronal Cholinergic System in Health and Disease

Release of non-neuronal acetylcholine from the human placenta: difference to neuronal acetylcholine

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