ATP-induced inhibition of gap junctional communication is enhanced by interleukin-1 β treatment in cultured astrocytes

• Published in: Neuroscience Vol. 126; no. 1; pp. 95 - 104
• Main Authors: Même, W, Ezan, P, Venance, L, Glowinski, J, Giaume, C
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2004; Elsevier; Elsevier - International Brain Research Organization
• Subjects: Adenosine Diphosphate - pharmacology; Adenosine Triphosphate - pharmacology; Animals; Astrocytes - cytology; Astrocytes - drug effects; Astrocytes - physiology; Biological and medical sciences; Cell Communication - drug effects; Cell Communication - physiology; Cells, Cultured; Cerebral Cortex - cytology; Connexin 43 - metabolism; Corpus Striatum - cytology; cytokines; Drug Synergism; Electric Conductivity; endothelin-1; Endothelin-1 - pharmacology; Fundamental and applied biological sciences. Psychology; Gap Junctions - physiology; glial cells; inflammation; intercellular communication; Interleukin-1 - pharmacology; Life Sciences; Mice; Neurobiology; Neurons and Cognition; nucleotides; Rats; Uridine Triphosphate - pharmacology; Vertebrates: nervous system and sense organs; PBS; glial cells; GJC; NP; Gj; IL-1β; [ATP] o; LY; EGTA; UTP; DMEM; ET-1; Cx43; inflammation; FBS; P2Y; RT-PCR; P2X; intercellular communication; 2Me-SATP; cytokines; endothelin-1; nucleotides; Glial cell; Neuroglia; Cytokine; Interleukin 1β; Endothelin 1; Inflammation; Astrocyte; Interleukin 1; ATP
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2004.03.031

Nucleotides are signaling molecules involved in variety of interactions between neurons, between glial cells as well as between neurons and glial cells. In addition, ATP and other nucleotides are massively released following brain insults, including inflammation, and may thereby be involved in mechanisms of cerebral injury. Recent concepts have shown that in astrocytes intercellular communication through gap junctions may play an important role in neuroprotection. Therefore, we have studied the effects of nucleotides on gap junction communication in astrocytes. Based on measurement of intercellular dye coupling and recording of junctional currents, the present study shows that ATP (10–100 μM) induces a rapid and a concentration-dependent inhibition of gap junction communication in cultured cortical astrocytes from newborn mice. Effects of agonists and antagonists of purinergic receptors indicate that the inhibition of gap junctional communication by ATP mainly involves the stimulation of metabotropic purinergic 1 (P2Y
1) receptors. Pretreatment with the pro-inflammatory cytokine interleukin-1β (10 ng/ml, 24 h), which has no effect by itself on gap junctional communication, increases the inhibitory effect of ATP and astrocytes become sensitive to uridine 5′-triphosphate (UTP). As indicated by the enhanced expression of P2Y
2 receptor mRNA, P2Y
2 receptors are responsible for the increased responses evoked by ATP and UTP in interleukin-1β-treated cells. In addition, the effect of endothelin-1, a well-known inhibitor of gap junctional communication in astrocytes was also exacerbated following interleukin-1β treatment.
We conclude that ATP decreases intercellular communication through gap junctions in astrocytes and that the increased sensitivity of gap junction channels to nucleotides and endothelin-1 is a characteristic feature of astrocytes exposed to pro-inflammatory treatments.