title: Pharmacological characterization of P2 purinoceptor types in rat locus coeruleus neurons.
abstract: The frequency of spontaneous action potentials of locus coeruleus neurons was recorded extracellularly in pontine slices of the rat brain. The adenosine 5'-triphosphate (ATP) analogues alpha,beta-methylene ATP (alpha,beta-meATP) and 2-methylthio ATP increased the firing rate with a similar potency, while uridine 5'-triphosphate (UTP) was inactive. Diadenosine 5'-pentaphosphate (Ap5A), diadenosine 5'-tetraphosphate (Ap4A) and diadenosine 5'-triphosphate (Ap3A) all facilitated the firing. When equimolar concentrations were compared, Ap5A had the largest effect followed by Ap4A and Ap3A. Suramin markedly inhibited responses to alpha,beta-meATP and 2-methylthio ATP; the effect of Ap4A was only slightly depressed by suramin. Pyridoxalphosphate-6-azophenyl-2,4-disulfonic acid (PPADS) strongly antagonized alpha, beta-meATP, but failed to alter the effects of 2-methylthio ATP and Ap4A. Reactive blue 2 weakly antagonized alpha,beta-meATP and did not interfere with 2-methylthio ATP and Ap4A. Moreover, suramin depressed responses to (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA), but not to substance P. PPADS failed to affect the AMPA- and NMDA-induced increases in firing. Hence, locus coeruleus neurons may possess receptors for adenosine nucleotides (P2X and P2Y purinoceptors) and dinucleotides (P2D purinoceptors); receptors for uridine nucleotides (P2U purinoceptors or pyrimidinoceptors) are probably absent.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Universität Freiburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Fröhlich
authors.forename: S
authors.initials: S
authors.lastname: Boehm
authors.forename: P
authors.initials: P
authors.lastname: Illes
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008125:Locus Coeruleus / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000187:drug effects*; D013498:Suramin / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology*
chemical_list: D011983:Receptors, Purinergic; D013498:Suramin; D000255:Adenosine Triphosphate; D000241:Adenosine; D014544:Uridine Triphosphate