PUBLICATION

Purinergic and adenosine receptors contribute to hypoxic hyperventilation in zebrafish (Danio rerio)

Authors
Coe, A.J., Picard, A.J., Jonz, M.G.
ID
ZDB-PUB-170926-10
Date
2017
Source
Comparative biochemistry and physiology. Part A, Molecular & integrative physiology   214: 50-57 (Journal)
Registered Authors
Jonz, Michael G.
Keywords
ATP, Adenosine, Chemical screen, Hypoxia, NEC, Neurotransmitter, P2X, Purinergic, Zebrafish
MeSH Terms
  • Animals
  • Behavior, Animal/drug effects
  • Biological Assay
  • Drug Evaluation, Preclinical
  • Gills/drug effects*
  • Gills/growth & development
  • Gills/metabolism
  • Hyperventilation/etiology
  • Hyperventilation/metabolism
  • Hyperventilation/prevention & control*
  • Hypoxia/physiopathology*
  • Kinetics
  • Larva/drug effects
  • Larva/growth & development
  • Larva/metabolism
  • Microscopy, Video
  • Protein Isoforms/antagonists & inhibitors
  • Protein Isoforms/metabolism
  • Pulmonary Ventilation/drug effects
  • Purinergic Antagonists/pharmacology*
  • Receptor, Adenosine A2A/chemistry
  • Receptor, Adenosine A2A/metabolism
  • Receptors, Purinergic P2X2/chemistry
  • Receptors, Purinergic P2X2/metabolism
  • Receptors, Purinergic P2X3/chemistry
  • Receptors, Purinergic P2X3/metabolism
  • Reproducibility of Results
  • Signal Transduction/drug effects*
  • Zebrafish/embryology
  • Zebrafish/metabolism*
  • Zebrafish Proteins/antagonists & inhibitors*
  • Zebrafish Proteins/metabolism
PubMed
28943320 Full text @ Comp. Biochem. Physiol. A Mol. Integr. Physiol.
Abstract
The chemoreceptors involved in oxygen sensing in teleost fish are neuroepithelial cells (NECs) in the gills, and are analogous to glomus cells in the mammalian carotid body. Purinergic signalling mechanisms involving the neurotransmitters, ATP and adenosine, have been identified in mediating hypoxic signalling in the carotid body, but these pathways are not well understood in the fish gill. The present study used a behavioural assay to screen for the effects of drugs, that target purinergic and adenosine receptors, on the hyperventilatory response to hypoxia in larval zebrafish (Danio rerio) in order to determine if the receptors on which these drugs act may be involved in hypoxic signalling. The purinergic receptor antagonist, PPADS, targets purinergic P2X2/3 receptors and inhibited the hyperventilatory response to hypoxia (IC50=18.9μM). The broad-spectrum purinergic agonist, ATPγS, elicited a hyperventilatory response (EC50=168μM). The non-specific adenosine receptor antagonist, caffeine, inhibited the hyperventilatory response to hypoxia, as did the specific A2a receptor antagonist, SCH58261 (IC50=220nM). These results suggest that P2X2/3 and A2a receptors are candidates for mediating hypoxic hyperventilation in zebrafish. This study highlights the potential of applying chemical screening to ventilatory behaviour in zebrafish to further our understanding of the pathways involved in signalling by gill NECs and oxygen sensing in vertebrates.
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