scholarly journals Purinergic signaling and the functioning of the nervous system cells

2015 ◽  
Vol 20 (5) ◽  
Author(s):  
Kamila Puchałowicz ◽  
Irena Baranowska-Bosiacka ◽  
Violetta Dziedziejko ◽  
Dariusz Chlubek

AbstractPurinergic signaling in the nervous system has been the focus of a considerable number of studies since the 1970s. The P2X and P2Y receptors are involved in the initiation of purinergic signaling. They are very abundant in the central and peripheral nervous systems, where they are expressed on the surface of neurons and glial cells - microglia, astrocytes, oligodendrocytes and Schwann cells and the precursors of the latter two. Their ligands - extracellular nucleotides - are released in the physiological state by astrocytes and neurons forming synaptic connections, and are essential for the proper functioning of nervous system cells. Purinergic signaling plays a crucial role in neuromodulation, neurotransmission, myelination in the CNS and PNS, intercellular communication, the regulation of ramified microglia activity, the induction of the response to damaging agents, the modulation of synaptic activity and other glial cells by astrocytes, and the induction of astrogliosis. Understanding these mechanisms and the fact that P2 receptors and their ligands are involved in the pathogenesis of diseases of the nervous system may help in the design of drugs with different and more effective mechanisms of action.

2011 ◽  
Vol 301 (5) ◽  
pp. L789-L794 ◽  
Author(s):  
Yu Gui ◽  
ZengYong Wang ◽  
XiaoRui Sun ◽  
Michael P. Walsh ◽  
Jing-Jing Li ◽  
...  

Contraction of airway smooth muscle (ASM) plays an important role in the regulation of air flow and is potentially involved in the pathophysiology of certain respiratory diseases. Extracellular nucleotides regulate ASM contraction via purinergic receptors, but the signaling mechanisms involved are not fully understood. Uridine adenosine tetraphosphate (Up4A) contains both pyrimidine and purine moieties, which are known to potentially activate P2X and P2Y receptors. Both P2X and P2Y receptors have been identified in the lung, including airway epithelial cells and ASM. We report here a study of purinergic signaling in the respiratory system, with a focus on the effect of Up4A on ASM contraction. Up4A induced contraction of rat isolated trachea and extrapulmonary bronchi as well as human intrapulmonary bronchioles. Up4A-induced contraction was blocked by di-inosine pentaphosphate, a P2X antagonist, but not by suramin, a nonselective P2 antagonist. Up4A-induced contraction was also attenuated by α,β-methylene-ATP-mediated P2X receptor desensitization. Several P2X receptors were detected at the mRNA level: P2X1, P2X4, P2X6, and P2X7, and to a lesser extent P2X3. Furthermore, the Up4A response was inhibited by removal of extracellular Ca2+ and by the presence of the L-type Ca2+ channel blocker, nifedipine, or the Rho-associated kinase inhibitor, H1152. We conclude that Up4A stimulates ASM contraction, and the underlying signaling mechanism appears to involve P2X (most likely P2X1) receptors, extracellular Ca2+ entry via L-type Ca2+ channels, and Ca2+ sensitization through the RhoA/Rho-associated kinase pathway. This study will add to our understanding of the pathophysiological roles of extracellular nucleotides in the lung.


2008 ◽  
Vol 294 (4) ◽  
pp. L733-L738 ◽  
Author(s):  
Yu Gui ◽  
Michael P. Walsh ◽  
Vera Jankowski ◽  
Joachim Jankowski ◽  
Xi-Long Zheng

Extracellular nucleotides, such as ATP, UDP, and UTP, regulate pulmonary vascular tone through P2X and P2Y receptors. Recently, uridine adenosine tetraphosphate (Up4A) was reported as a novel endothelium-derived vasoconstrictive factor. Up4A contains both purine and pyrimidine moieties, which potentially activate P2X and P2Y receptors. The present study examined the effect of Up4A on contractility of isolated rat pulmonary artery. Up4A at 1–100 μM stimulated contraction in a concentration-dependent manner. Up4A was equipotent as UTP and UDP in the endothelium-denuded artery while much more effective than UTP and UDP in endothelium-intact preparations. The vasoconstrictor effect of Up4A was inhibited by suramin but not IP5I or desensitization of P2X receptors with α,β-methylene-ATP (α,β-Me-ATP). Up4A-induced contraction was also inhibited by pretreatment with thapsigargin, nitrendipine, or EGTA but unaffected by H1152. Furthermore, unlike ATP and UTP, Up4A did not induce relaxation of endothelium-intact preparations precontracted with phenylephrine. These results suggest that Up4A is a potent vasoconstrictor, but not a vasodilator, of the rat pulmonary artery. Up4A likely acts through a suramin-sensitive P2Y receptor. The contractile effect of Up4A involves the entry of extracellular Ca2+ and release of Ca2+ from intracellular stores but not Ca2+ sensitization via the RhoA/Rho kinase pathway. Up4A, therefore, potentially plays an important role in the regulation of pulmonary vascular tone.


Glia ◽  
2021 ◽  
Author(s):  
Jennifer Patritti‐Cram ◽  
Robert. A. Coover ◽  
Michael P. Jankowski ◽  
Nancy Ratner

1990 ◽  
Vol 64 (5) ◽  
pp. 1390-1399 ◽  
Author(s):  
M. M. Segal ◽  
E. J. Furshpan

1. Microcultures were grown containing small numbers of hippocampal neurons. The neurons grew on glial cells attached to patches of either collagen or palladium. A layer of agarose underlying the microcultures prevented connections from forming between nearby microcultures. 2. Neurons formed strong chemical synaptic connections within each microculture, with monosynaptic fast-excitatory, fast-inhibitory, and slow-inhibitory synaptic actions. 3. Small networks with as few as two neurons generated epileptiform activity that closely resembled the epileptiform activity seen in mass cultures containing thousands of neurons. The epileptiform activity was observed when microcultures that were grown for weeks in blockers of synaptic activity (kynurenate and elevated Mg2+) were washed free of these blockers. 4. Such a microculture technique allows study of epileptiform activity in a simplified system and facilitates analysis of the synaptic actions underlying the epileptiform activity.


2014 ◽  
Vol 15 (12) ◽  
pp. 23672-23704 ◽  
Author(s):  
Kamila Puchałowicz ◽  
Maciej Tarnowski ◽  
Irena Baranowska-Bosiacka ◽  
Dariusz Chlubek ◽  
Violetta Dziedziejko

Author(s):  
Cristiana Pistono ◽  
Nea Bister ◽  
Iveta Stanová ◽  
Tarja Malm

Glial cells are crucial for the maintenance of correct neuronal functionality in a physiological state and intervene to restore the equilibrium when environmental or pathological conditions challenge central nervous system homeostasis. The communication between glial cells and neurons is essential and extracellular vesicles (EVs) take part in this function by transporting a plethora of molecules with the capacity to influence the function of the recipient cells. EVs, including exosomes and microvesicles, are a heterogeneous group of biogenetically distinct double membrane-enclosed vesicles. Once released from the cell, these two types of vesicles are difficult to discern, thus we will call them with the general term of EVs. This review is focused on the EVs secreted by astrocytes, oligodendrocytes and microglia, aiming to shed light on their influence on neurons and on the overall homeostasis of the central nervous system functions. We collect evidence on neuroprotective and homeostatic effects of glial EVs, including neuronal plasticity. On the other hand, current knowledge of the detrimental effects of the EVs in pathological conditions is addressed. Finally, we propose directions for future studies and we evaluate the potential of EVs as a therapeutic treatment for neurological disorders.


2010 ◽  
Vol 6 (1) ◽  
pp. 31-42 ◽  
Author(s):  
Giovanni Villa ◽  
Marta Fumagalli ◽  
Claudia Verderio ◽  
Maria P. Abbracchio ◽  
Stefania Ceruti

The role of adenosine-5′-triphosphate (ATP) and of the ligand-gated P2X3receptor in neuronal dorsal root ganglia (DRG) pain transmission is relatively well established. Much less is known about the purinergic system in trigeminal ganglia (TG), which are involved in certain types of untreatable neuropathic and inflammatory pain, as well as in migraine. Emerging data suggest that purinergic metabotropic P2Y receptors on both neurons and satellite glial cells (SGCs) may also participate in both physiological and pathological pain development. Here, we provide an updated literature review on the role of purinergic signaling in sensory ganglia, with special emphasis on P2Y receptors on SGCs. We also provide new original data showing a time-dependent downregulation of P2Y2and P2Y4receptor expression and function in purified SGCs cultures from TG, in comparison with primary mixed neuron–SGCs cultures. These data highlight the importance of the neuron–glia cross-talk in determining the SGCs phenotype. Finally, we show that, in mixed TG cultures, both adenine and guanosine induce intracellular calcium transients in neurons but not in SGCs, suggesting that also these purinergic-related molecules can participate in pain signaling. These findings may have relevant implications for the development of new therapeutic strategies for chronic pain treatment.


Author(s):  
Wiktor Djaczenko ◽  
Carmen Calenda Cimmino

The simplicity of the developing nervous system of oligochaetes makes of it an excellent model for the study of the relationships between glia and neurons. In the present communication we describe the relationships between glia and neurons in the early periods of post-embryonic development in some species of oligochaetes.Tubifex tubifex (Mull. ) and Octolasium complanatum (Dugès) specimens starting from 0. 3 mm of body length were collected from laboratory cultures divided into three groups each group fixed separately by one of the following methods: (a) 4% glutaraldehyde and 1% acrolein fixation followed by osmium tetroxide, (b) TAPO technique, (c) ruthenium red method.Our observations concern the early period of the postembryonic development of the nervous system in oligochaetes. During this period neurons occupy fixed positions in the body the only observable change being the increase in volume of their perikaryons. Perikaryons of glial cells were located at some distance from neurons. Long cytoplasmic processes of glial cells tended to approach the neurons. The superimposed contours of glial cell processes designed from electron micrographs, taken at the same magnification, typical for five successive growth stages of the nervous system of Octolasium complanatum are shown in Fig. 1. Neuron is designed symbolically to facilitate the understanding of the kinetics of the growth process.


Sign in / Sign up

Export Citation Format

Share Document