Regional and cellular distribution of the P2Y1 purinergic receptor in the human brain: Striking neuronal localisation

✍ Scribed by Moore, Darren; Chambers, Jon; Waldvogel, Henry; Faull, Richard; Emson, Piers

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 545 KB
• Volume: 421
• Category: Article
• ISSN: 0021-9967
• DOI: 10.1002/(sici)1096-9861(20000605)421:3<374::aid-cne6>3.0.co;2-z

✦ Synopsis

The biological actions of extracellular nucleotides are exerted via two families of P2 receptors, P2X and P2Y. The metabotropic P2Y receptors comprise at least 7 distinct subtypes, which have been cloned from a number of species. However, none of the P2Y receptor proteins have been visualised yet in human brain. In the present study, the regional and cellular distribution of the P2Y 1 receptor was investigated in the human brain by using immunohistochemistry. Polyclonal antibodies were raised against a synthetic peptide from the C-terminus of the P2Y 1 protein. Immunoblot analysis demonstrated that P2Y 1 antiserum specifically recognised a 63-kDa band in human and rat brain membranes. Similarly, the antiserum specifically detected the human P2Y 1 receptor in transfected 1321N1 cells. Immunohistochemical analysis on perfusion-fixed human brain tissue showed a widespread distribution for this receptor throughout the brain. At the cellular level, the P2Y 1 receptor was strikingly localised to neuronal structures of the cerebral cortex, cerebellar cortex, hippocampus, caudate nucleus, putamen, globus pallidus, subthalamic nucleus, red nucleus, and midbrain. Expression of the P2Y 1 receptor was not detected in other non-neuronal cell types. These results provide the first characterisation of the cellular distribution of a P2Y receptor in the human brain. The widespread and abundant distribution of the P2Y 1 receptor suggests its involvement in a number of important functions within the human brain. The neuronal localisation of this receptor points towards a possible role in neurotransmission, and also highlights a major role for extracellular nucleotides as signaling molecules within the brain.