Юрий Шмуклер

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Changes in the physiological roles of neurotransmitters during individual development

Neuroscience and Behavioral Physiology, 1999

The classical neurotransmitters (acetylcholine and biogenic monoamines) are multifunctional subst... more The classical neurotransmitters (acetylcholine and biogenic monoamines) are multifunctional substances involved in intra- and intercellular signaling at all stages of ontogenesis in multicellular animals. A cyclical scheme is proposed to describe age-related changes in neurotransmitter functions at different stages of development from oocyte maturation to neuron formation. This may reflect not only the temporospatial organization of neurotransmitter processes, but also the origin of the functions of acetylcholine and biogenic monoamines from the protosynapses of the cleaved embryo to neuronal synapses.

Expression of transmitter receptor genes in early development of sea urchin Paracentrotus lividus

Russian Journal of Developmental Biology, May 1, 2012

Neurotransmitters (including serotonin and acetylcholine) perform a number of prenervous function... more Neurotransmitters (including serotonin and acetylcholine) perform a number of prenervous functions in early sea urchin development. To detect the particular receptor components involved in these processes, we carried out a database search and nucleotide sequences homologous to serotonin receptor type 4, and the alpha6- and alpha10-subunits of nicotinic acetylcholine receptor were found among EST-clones from early Paracentrotus lividus embryos. Expression of these transcripts during early development was demonstrated using RT-PCR. These results are the first molecular biology evidence ofserotonin and acetylcholine receptor expression in sea urchin early embryogenesis.

On the Intracellular Transmitter Reception

Neurochemical Journal, Oct 1, 2018

⎯The idea on the possibility of intracellular neurotransmitter receptor localization exists alrea... more ⎯The idea on the possibility of intracellular neurotransmitter receptor localization exists already more than half a century, however it remains disputable until now. The data on such neurotransmitter receptors' localization in unicellular organisms, early (pre-nervous) embryos and in adult cells, including neurons are summarized in the present paper. These data were obtained both using pharmacological experiments with pairs of hydrophilic and lipophilic analogues of transmitter receptor ligands, by direct ligand microinjection into the cells, and also as by labelled ligand binding and using electrophysiological methods. The data on the intracellular localization of transmitter receptors provokes to critically evaluate the current understanding of the origin of transmitter substances and corresponding receptors. It is suggested that they were formed as the result of the evolution of function of systems that originally were coupled to the processes of intracellular syntheses but not to cellular interactions.

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The influence of second messengers and related substances on the sensitivity of early embryos to cytostatic neurochemicals

Comparative Biochemistry and Physiology Part C: Comparative Pharmacology, 1986

1 "Prenervous" neurotransmitters interact with second messengers in the regulation of early embry... more 1 "Prenervous" neurotransmitters interact with second messengers in the regulation of early embryogenesis of sea urchins and the clawed frog Xenopus laevis. 2. Propranolol and atropine inhibit cleavage divisions of X. lueuis only after their intracellular administration. 3. The level of the membrane potential (including a zero level) of the embryos studied is not essential for the cleavage divisions. 4. Possible mechanisms of action of the "prenervous" neurotransmitters at the intracellular level and their coupling with second messengers are discussed.

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Changes in the physiological roles of neurotransmitters during individual development

Neuroscience and Behavioral Physiology, 1999

The Serotonin System in Mammalian Oogenesis

Neuroscience and Behavioral Physiology, 2022

Transmitters, particularly serotonin, not only have the classical function of transmitting nerve ... more Transmitters, particularly serotonin, not only have the classical function of transmitting nerve impulses, but also take part in a whole series of regulatory processes throughout ontogeny, including those occurring long before formation of the nervous system. The structure and function of the serotonin system in mammalian oogenesis are considered, along with the sources and mechanisms of accumulation of the transmitter in oocytes and the expression of the components of the serotonin system – receptors, synthesis and degradation enzymes, and membrane and vesicular transporters in cells in the female mammalian reproductive system. Data on the influences of serotonin reuptake inhibitors (SERT) on oogenesis and embryogenesis are presented.

A “micromere model” of cell-cell interactions in sea urchin early embryos

Biophysics, Jun 1, 2010

Serotonin and acetylcholine modulate the sensitivity of early sea urchin embryos to protein kinase C activators

Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, Jul 1, 1998

The protein kinase C activators 1-oleoyl-2-acetyl-rac-glycerol (OAG) and phorbol 12-myristate 13-... more The protein kinase C activators 1-oleoyl-2-acetyl-rac-glycerol (OAG) and phorbol 12-myristate 13-acetate (PMA) evoke similar developmental anomalies in early embryos of sea urchins, that is, block of cleavage divisions, formation of giant polyploid nuclei with nucleolus-like inclusions, damage of cortical microfilaments and extrusion of small cytoplasts (mini-cells). Protein kinase inhibitors belonging to two different chemical groups (derivatives of isoquinoline and naphthalene) protect the embryos against OAG and PMA action. Some of these inhibitors (H-7, H-8, and H-9) also weaken the effects of 5-HT antagonists. 5-HT weakens and acetylcholine (ACh) potentiates the developmental anomalies evoked by PMA and OAG. It is suggested that endogenous 5-HT and ACh of early sea urchin embryos are functionally coupled with second messenger systems acting through the regulation of protein kinase C activity.

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Effect of cyclic nucleotides on sensitivity of early sea urchin embryos to cytotoxic neuropharmacological drugs

Bulletin of Experimental Biology and Medicine, Mar 1, 1984

It has been shown that cytotoxic action of neuropharmacological drugs (transmitter antagonists) o... more It has been shown that cytotoxic action of neuropharmacological drugs (transmitter antagonists) on early urchin embryos is reduced or abolished by cyclic nucleotides and sodium fluoride. Such a protective action differs in cAMP and dibutyryl analogs of cyclic nucleotides, depending on the chemical structure of an embryotoxic substance. It is suggested that, endogenous intracellular &quot;prenervous&quot; transmitters and cyclic nucleotides are interrelated in the regulation of cell division in urchin embryos.

Expression of Components of the Serotonergic System in Folliculogenesis and Preimplantation Development in Mice

Russian Journal of Developmental Biology, 2018

The functions of serotonin include the growth and development regulation of female germ cells as ... more The functions of serotonin include the growth and development regulation of female germ cells as well as early embryo development. RT-PCR analysis of mRNA expression of the genes of the enzymes for synthesis and degradation and transporters and receptors of serotonin during folliculogenesis and preimplantation development of mice was performed to discover the particular mechanisms of these functions. The mRNA of tryptophan hydroxylase tph1 and monoaminoxidase maoa; membrane transporter sert and vesicular transporter vmat2; and serotonin receptors htr1b, htr1d, htr2a, htr5b, and htr7 were revealed in granulosa cells. The expression of mRNA of the aromatic amino acid decarboxylase ddc and the htr2b receptor additionally appears in the yellow body. The expression of mRNA of the genes of the tph2, ddc, and maoa enzymes; the sert, vmat1, and vmat2 transporters; and quite a number of receptors is observed during the preimplantation development, and it is transitory in most of them. The expression of all components and its dynamics suggest that the serotonergic signaling system is functionally active in mouse folliculogenesis and preimplantation development.

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Nicotinic antagonists (piperidines and quinuclidines) reduce the susceptibility of early sea urchin embryos to agents evoking calcium shock

General Pharmacology: The Vascular System, 1997

1. Some nicotinic antagonists (piperidine and quinuclidine derivatives and bis-quaternary compoun... more 1. Some nicotinic antagonists (piperidine and quinuclidine derivatives and bis-quaternary compounds) protect early embryos of the sea urchin Lytechinus pictus against a calcium shock evoked by ionomycin or a mixture of phorbol myristate acetate and nicotine. 2. Maximal protective potency was found for drugs that did not penetrate the plasma membrane. 3. Early sea urchin embryos have nicotinic acetylcholine receptors (nAChR) or nAChR-like structures localized on the cell surface that, apparently, take part in the control of Ca2+ influx.

Effect of local microapplication of serotonergic drugs on membrane currents of Paracentrotus lividus early embryos

Russian Journal of Developmental Biology, 2007

5-HT-receptive structures are localized in the interblastomere cleft ofParacеntrotus lividusearly embryos

Zygote, 2008

SummaryLocal application of the agonists of serotonin receptors of third type 5-HTQ, SR57277A and... more SummaryLocal application of the agonists of serotonin receptors of third type 5-HTQ, SR57277A and quipazine into the interblastomere cleft of the sea urchinParacentrotus lividusembryo during first cleavage division, evokes specific membrane currents, whereas application of these drugs out of contact area show currents of lower amplitude and longer latent period. At the same time 5-HT3-receptor agonist quipazine imitates interblastomere signal in half embryos, but corresponding antagonists prevent it. Present data develop the hypothesis of protosynapse, demonstrating that the distribution of membrane serotonin receptors is limited to the period of cleavage division and localized in the interblastomere contact area. A possible role of spatial–temporal restriction of receptors at the interblastomere contact area is discussed in relation to the subsequent embryo development.

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Uptake and Metabolization of Serotonin by Granulosa Cells Form a Functional Barrier in the Mouse Ovary

International Journal of Molecular Sciences, Nov 27, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more

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Effects of Haloperidol and Cyproheptadine on the Cytoskeleton of the Sea Urchin Embryos

Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology, 2020

Abstract Early sea urchin embryos are sensitive to agonists and antagonists of transmitter recept... more Abstract Early sea urchin embryos are sensitive to agonists and antagonists of transmitter receptors, both metabotropic and channel ones. In this work, we studied mechanisms of the cytostatic action of cyproheptadine and haloperidol–antagonists of serotonin 5HT 2 receptors and dopamine D 2 receptors, respectively. For this purpose, we employed the model of the blockade of the first cleavage division in sea urchin, which allows quantifying the effects of embryotoxic substances. The action of haloperidol and cyproheptadine is mediated by the effects on cytoskeleton elements. Both antagonists caused an increase in the degree of polymerization of the actin cytoskeleton, both in the cortical layer and in the cytoplasm. In addition, both antagonists affected the tubulin cytoskeleton: haloperidol predominantly disturbed spatial organization of the mitotic spindle, while cyproheptadine caused a complete depolymerization of tubulin and arrest of mitotic processes. The results indicate that cytostatic effects of dopamine and serotonin antagonists on cleavage divisions of sea urchin embryos are mediated by similar and/or crosstalk molecular mechanisms but also have significant differences that require further research.

Possible role of ?prenervous? neurotransmitters in cellular interactions of early embryogenesis: A hypothesis

Neurochemical Research, 1981

Evidence is presented in support of the working hypothesis that "prenervous" neurotransmitters di... more Evidence is presented in support of the working hypothesis that "prenervous" neurotransmitters directly participate in cell-cell interactions occurring during the first several cleavage divisions of sea urchin embryos, a function which may occur during the early development of higher animals as well. This intercellular signaling could be a link in the evolutionary progression from the use of these substances as intracellular regulators to their participation in cell-cell interactions occurring during synaptic transmission.

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Non-Neuronal Transmitter Systems in Bacteria, Non-Nervous Eukaryotes, and Invertebrate Embryos

Biomolecules, 2022

In 1921, Otto Loewi published his report that ushered in the era of chemical transmission of biol... more In 1921, Otto Loewi published his report that ushered in the era of chemical transmission of biological signals. January 2021 marked the 90th anniversary of the birth of Professor Gennady A. Buznikov, who was the first to study the functions of transmitters in embryogenesis. A year earlier it was 60 years since his first publication in this field. These data are a venerable occasion for a review of current knowledge on the mechanisms related to classical transmitters such as 5-hydroxytryptamine, acetylcholine, catecholamines, etc., in animals lacking neural elements and prenervous invertebrate embryos.

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Oocyte-Mediated Effect of Serotonin on the Functional Status of Granulosa Cells

Russian Journal of Developmental Biology, 2021

In the mammalian ovary, serotonin has all the components necessary for its signaling function and... more In the mammalian ovary, serotonin has all the components necessary for its signaling function and affects the functional activity of granulosa cells. At the same time, the accumulation of serotonin with the help of a specific SERT transporter occurs mainly in the oocytes of growing ovarian follicles and is hardly present in granulosa cells. Quantitative analysis of mRNA expression of markers of proliferation, apoptosis, and functional state of follicular cells, as well as oocyte growth factors, was performed on an experimental model of ovarian follicle culture. Serotonin (1 µM) does not exhibit pronounced mitogenic and pro- and antiapoptotic properties and does not affect the expression of steroidogenesis markers. At the same time, serotonin stimulates the expression of cyclin genes Ccnd1, Ccnd2, and Ccne1 and also Has2, Ptgs2, Ptgfr, Igfbp, and Ihh in granulosa cells. Also, the addition of serotonin leads to an increase in the expression of Gdf9 in oocytes. There is a more pronounc...

Action of serotonin antagonists on cytoplasmic calcium levels in early embryos of sea urchin Lytechinus pictus

The International journal of developmental biology, 1999

Possible interaction of the serotonergic system with intracellular calcium mechanisms was investi... more Possible interaction of the serotonergic system with intracellular calcium mechanisms was investigated using techniques of ratio imaging measurement of intracellular Ca2+ and confocal microscopy in cleaving embryos of sea urchin Lytechinus pictus. Some serotonin antagonists specifically increase free intracellular Ca2+ and evoke transient regression of the first cleavage furrow, suggesting possible linkage of serotonergic and calcium mechanisms in the regulation of cellular events during cleavage divisions. These effects were more pronounced in the experiments with hydrophilic 5-HT-antagonists, quarternary ammonium salts that do not penetrate the cell membrane. Thus, it appears that 5-HT-receptors which mediate these effects are localised on the cell membrane, whereas previously studied receptors mediating the cytostatic action of lipophilic 5-HT-antagonists are localised intracellularly.

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Expression dynamics of the serotonergic system components in granulosa cells of the developing ovarian follicle and after luteinization

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