Emerging challenges of assigning P2X7 receptor function and immunoreactivity in neurons.
Currently available antibodies to the P2X(7) receptor are unreliable determinants of neuronal P2X(7) immunoreactivity, owing to staining of a "P2X(7)-like" protein that is not eliminated by legitimate P2X(7) gene-knockout approaches. Despite this, compelling electrophysiological and pharmacological data strongly support a role for P2X(7) receptors in neuronal function and injury. A major priority for the field now is to identify the neuronal "P2X(7)-like" protein and develop effective antibodies selective for neuronal P2X(7) immunoreactivity. Until this occurs, we are dependent on rigorous application of multiple pharmacological criteria for attribution of neuronal function to P2X(7) receptors in non-human tissues, including greater activity in response to BzATP than to ATP, sensitivity to blockade by nanomolar concentrations of Brilliant Blue-G, irreversible antagonism by periodate-oxidized ATP, and lack of inhibition by suramin.
Department of Pharmacology and Therapeutics, University of Manitoba and Division of Neurodegenerative Disorders, St Boniface Hospital Research Center, Winnipeg, Canada R2H 2A6. canderson@sbrc.ca
Christopher M
CM
Anderson
Maiken
M
Nedergaard
D000255:Adenosine Triphosphate / Q000276:immunology; D000818:Animals; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001921:Brain / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009474:Neurons / Q000276:immunology / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000276:immunology* / Q000378:metabolism; D058486:Receptors, Purinergic P2X7; D009435:Synaptic Transmission / Q000502:physiology; D014018:Tissue Distribution
C546468:P2RX7 protein, human; C546469:P2rx7 protein, mouse; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate