Pharmacological characterization of P-2 purinoceptor types in rat locus coeruleus neurons

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 (Ap(5)A), diadenosine 5'-tetraphosphate (Ap(4)A) and diadenosine 5'-triphosphate (Ap(3)A) all facilitated the firing. When equimolar concentrations were compared, Ap(5)A had the largest effect followed by Ap(4)A and Ap(3)A. Suramin markedly inhibited responses to alpha,beta-meATP and 2-methylthio ATP; the effect of Ap(4)A was only slightly depressed by suramin. Pyridoxalphosphate-6-azophenyl-2,3-disulfonic acid (PPADS) strongly antagonized alpha,beta-meATP, but failed to alter the effects of 2-methylthio ATP and Ap(4)A. Reactive blue 2 weakly antagonized alpha,beta-meATP and did not interfere with 2-methylthio ATP and Ap(4)A. 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 (P-2X and P-2Y purinoceptors) and dinucleotides (P-2D purinoceptors); receptors for uridine nucleotides (P-2U purinoceptors or pyrimidinoceptors) are probably absent.