title: The P2Y(1) receptor closes the N-type Ca(2+) channel in neurones, with both adenosine triphosphates and diphosphates as potent agonists.
abstract: The rat P2Y(1) nucleotide receptor, the P2Y subtype abundant in the brain, was heterologously expressed in rat superior cervical ganglion neurones by micro-injection of the receptor cRNA or cDNA. ADP inhibited the N-type Ca(2+) current by 64%, with EC(50) 8.2 nM, an action blocked competitively by the P2Y(1) receptor antagonist adenosine 3', 5'-bis-phosphate (K(i) 0.7 microM). 2-Methylthio-ADP inhibited the Ca(2+) current likewise, but with EC(50) 0.57 nM, giving the highest potency reported therewith for P2Y(1). Significantly, ATP and 2-methylthio-ATP were also agonists, the latter again at a very high potency (EC(50) 2.5 nM). We propose that this neuronal receptor, when present in brain at a high density as at synapses, can respond to very low concentrations of ATP and ADP as agonists, and that this would result in inhibition of N-type Ca(2+) currents and hence can reduce transmitter release or increase neuronal excitability.
authors.affiliation: Department of Pharmacology, University College London, Gower Street, London WC1E 6BT. Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJ, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: Filippov
authors.forename: D A
authors.initials: DA
authors.lastname: Brown
authors.forename: E A
authors.initials: EA
authors.lastname: Barnard
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001254:Astrocytoma / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D058910:Purinergic P2 Receptor Agonists; D012313:RNA / Q000096:biosynthesis / Q000494:pharmacology; D051381:Rats; D058472:Receptors, Purinergic P2Y1; D015398:Signal Transduction / Q000187:drug effects; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; C546384:P2ry1 protein, rat; D058910:Purinergic P2 Receptor Agonists; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides; D000244:Adenosine Diphosphate; D012313:RNA; D000255:Adenosine Triphosphate; C008501:2-methylthio-ATP