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- Title
Extended pharmacological profiles of rat P2Y[sub2] and rat P2Y[sub4] receptors and their sensitivity to extracellular H[sup+] and Zn²[sup+] ions.
- Authors
Wildman, Scott S.; Unwin, Robert J.; King, Brian F.
- Abstract
1 Two molecularly distinct rat P2Y receptors activated equally by adenosine-5'-triphosphate (ATP) and uridine-5'-triphosphate (UTP) (rP2Y[sub2;] and rP2Y[sub4] receptors) were expressed in Xenopus oocytes and studied extensively to find ways to pharmacologically distinguish one from the other. 2 Both P2Y subtypes were activated fully by a number of nucleotides. Tested nucleotides were equipotent at rP2Y[sub4] (ATP= UTP=CTP=GTP=ITP), but not at rP2Y[sub2] (ATP = UTP>CTP>GTP>ITP), For dinucleotides (Ap[subn]A n=2-6), rP2Y[sub4] was only fully activated by Ap[sub4]A. which was as potent as ATP. All tested dinucleotides. except for Ap[sub2]A. fully activated rP2Y[sub2]. hut none were as potent as ATP. ATPγS and BzATP fully aetivated rP2Y[sub2]. whereas ATPγS was a weak agonist and BzATP was inactive (as an agonist) at rP2Y[sub4] receptors. 3 Each P2Y subtype showed different sensitivities to known P2 receptor autagonists, For rP2Y[sub2]. the potency order was suramin> > PPADS= RB-2> TNP-ATP and suramin was a eompetitive antagonist (pA[sub2], 5.40). For rP2Y[sub4], the order was RB-2> >suramin > PPADS> TNP-ATP and RB-2 was a competitive antagonist (pA[sub2], 6.43). Also. BzATP was an antagonist at rP2Y[sub4] receptors. 4 Extracellular acidification (from pH 8.0 to pH 5.5) enhanced the potency of ATP and UTP by 8- 10-fold at rP2Y[sub4] but did not affect agonist responses at rP2Y[sub2] receptors. 5 Extracellular Zn[sup2+] ions (0.1-300μM coapplied with ATP inhibited agonist responses at rP2Y[sub4] but not at rP2Y[sub2] receptors. 6 These two P2Y receptors differ significantly in terms of agonist and antagonist profiles, and the modulatory activities of extracellular H[sup+] and Zn[7sup2+;] ions. These pharmacological differences will help to distinguish between rP2Y[sub2] and rP2Y[sub4] receptors, in vivo.
- Subjects
PURINERGIC receptors; EXTRACELLULAR fluid; PURINE nucleotides; PYRIMIDINE nucleotides; G proteins; ZINC; IONS; XENOPUS
- Publication
British Journal of Pharmacology, 2003, Vol 140, Issue 7, p1177
- ISSN
0007-1188
- Publication type
Article
- DOI
10.1038/sj.bjp.0705544