Research article summary (published 8 Oct 2009):

Increase of intracellular Ca2+ by P2Y but not P2X receptors in cultured cortical multipolar neurons of the rat.

Full Abstract

The expression and functionality of P2X/P2Y receptor subtypes in multipolar nonpyramidal neurons of mixed cortical cell cultures were investigated by means of immunocytochemistry and fura-2 microfluorimetry. The morphological studies revealed that most of the neurons are immunoreactive for GABA and express a range of P2X/P2Y receptors, predominantly of the P2X(2,4,6) and P2Y(1,2) subtypes. P2X(1) and P2X(7) receptor immunoreactivity (IR) was found on thin axon-like processes and presynaptic structures, respectively. Application of ATP caused a small concentration-dependent increase in intracellular Ca2+ concentration ([Ca2+]i) in most investigated neurons, whereas only about the half of these cells responded to 2',3'-O-(benzoyl-4-benzoyl)-ATP (BzATP), ADPbetaS, 2MeSADP, or 2MeSATP and even fewer cells to UTP. In contrast, alpha,beta-meATP, UDP, and UDP-glucose failed to produce any [Ca2+]i signaling. The response to ATP itself was inhibited by pyridoxal-5'-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), Reactive Blue 2, 2'-deoxy-N(6)-methyl adenosine 3',5'-diphosphate (MRS2179), and suramin (300 microM) as well as by a cyclopiazonic acid-induced depletion of intracellular Ca2+ stores. A Ca2+-free external medium tended to decrease the ATP-induced [Ca2+]i transients, although this action did not reach statistical significance. Various blockers of voltage-sensitive Ca2+ channels and the gap junction inhibitor carbenoxolone did not interfere with the effect of ATP, whereas a combination of the ionotropic glutamate receptor antagonists D(-)-2-amino-5-phosphonopentanoic acid (AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) decreased it. Cross-desensitization experiments between ADPbetaS or UTP and ATP suggested that ATP acts on the one hand via P2Y(1,2) receptors and on the other hand by additional signaling mechanisms. These mechanisms may involve the release of glutamate (which in consequence activates ionotropic glutamate receptors) and the entry of Ca2+ via store-operated Ca2+ channels. Evidence for the presence of functional P2X receptors, in particular P2X(7), remains elusive.

Author information

Author/s: Fischer, Wolfgang (W); Nörenberg, Wolfgang (W); Franke, Heike (H); Schaefer, Michael (M); Illes, Peter (P);

Affiliation: Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Haertelstrasse 16-18, Leipzig D-04107, Germany. fisw(-atsign-)medizin.uni-leipzig.de

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of comparative neurology (J Comp Neurol), published in United States. (Language: eng)

Reference: 2009-Oct; vol 516 (issue 5) : pp 343-59

Dates: Created 2009/08/13; Completed 2009/10/23;

PMID: 19655384, status: MEDLINE (last retrieval date: 10/23/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adenosine Triphosphate - antagonists & inhibitors; pharmacology Animals Calcium - metabolism Cells, Cultured Cerebral Cortex - cytology; drug effects Data Interpretation, Statistical Excitatory Amino Acid Agonists - pharmacology Female Fluorescent Dyes Fluorometry

Lysine - analogs & derivatives Microtubule-Associated Proteins - metabolism Neuroglia - metabolism Neurons - metabolism Pregnancy Rats Rats, Wistar Receptors, Glutamate - drug effects Receptors, Purinergic P2 - drug effects; genetics; physiology gamma-Aminobutyric Acid - pharmacology

Associated Chemicals: Excitatory Amino Acid Agonists (0) ; Fluorescent Dyes (0) ; Microtubule-Associated Proteins (0) ; Mtap2 protein, rat (0) ; Receptors, Glutamate (0) ; Receptors, Purinergic P2 (0) ; gamma-Aminobutyric Acid (56-12-2) ; Adenosine Triphosphate (56-65-5) ; Lysine (56-87-1) ; biocytin (576-19-2) ; Calcium (7440-70-2)

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