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The discovery and development of P2 receptor subtypes
1Department of Physiology and Pharmacology, Strathclyde Institute of Biomedical Research, University of Strathclyde, 27 Taylor Street, G4 0NR, Glasgow, UK. c.kennedy@strath.ac.uk
Journal of the Autonomic Nervous System
|June 28, 2000
Summary
Extracellular nucleotides bind to P2 receptors, which were first identified in 1978. Research has since classified these receptors into subtypes, with 12 mammalian P2 receptor subtypes cloned and functionally expressed.
Area of Science:
- Pharmacology
- Molecular Biology
- Cellular Signaling
Background:
- Extracellular purine and pyrimidine nucleotides regulate cellular functions via P2 receptors.
- The P2-purinoceptor was identified in 1978, followed by pharmacological subdivision into P2X and P2Y subtypes in the 1980s.
- Further characterization identified P2T, P2Z, P2U, and P2D purinoceptors.
Purpose of the Study:
- To review the historical classification and recent molecular characterization of P2 receptors.
- To bridge the gap between cloned mammalian P2 receptor subtypes and their native counterparts in various tissues.
Main Methods:
- Pharmacological characterization of native receptors.
- Functional studies on native receptors.
- Molecular cloning and functional expression of mammalian P2 receptor subtypes.
Main Results:
- Identification and initial characterization of the P2-purinoceptor in 1978.
- Pharmacological subdivision into P2X and P2Y subtypes.
- Cloning and functional expression of at least 12 mammalian P2 receptor subtypes in the 1990s.
Conclusions:
- Significant progress has been made in identifying and classifying P2 receptor subtypes.
- The current challenge lies in correlating molecularly defined recombinant receptors with native receptors found in diverse tissues.