EXCITATORY EFFECTS OF ADENOSINE 5'-TRIPHOSPHATE ON RAT LOCUS-CERULEUS NEURONS

Pontine slices of the rat brain were used for extracellular recording of the frequency of spontaneous action potentials of locus coeruleus (LC) neurones. In the absence of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), alpha,beta-methyleneadenosine 5'-triphosphate (alpha,beta-meATP; 0.3-30-mu-mol/l) and 2-methylthio ATP (0.3-100-mu-mol/l), but not ATP (1-100-mu-mol/l) increased the firing rate. In the presence of DPCPX 0.1-mu-mol/l, all three purinoceptor agonists were active, the potency order being alpha-beta-meATP > 2-methylthio ATP = ATP. Preincubation of the slices with tetrodotoxin (TTX) 0.5-mu-mol/l decreased the spike discharge but did not alter the percent facilitatory effect of alpha,beta-meATP 30-mu-mol/l. There was no desensitization to alpha,beta-meATP 10-mu-mol/l on repeated or continuous application. Suramin 100-mu-mol/l selectively depressed the effect of alpha,beta-meATP 30-mu-mol/l without interfering with the effect of equiactive concentrations (10-100-mu-mol/l) of glutamic acid. The concentration-response curve of alpha,beta-meATP was shifted in a parallel manner to the right by suramin 10-mu-mol/l. While DPCPX 0.1-mu-mol/l facilitated firing, suramin 100-mu-mol/l did not change it. In conclusion, LC neurones may possess P2-purinoceptors of an unidentified type, which share some P2x characteristics.