Excitatory effects of adenosine 5'-triphosphate on rat locus coeruleus neurones

Abstract

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 mumol/l) and 2-methylthio ATP (0.3-100 mumol/l), but not ATP (1-100 mumol/l) increased the firing rate. In the presence of DPCPX 0.1 mumol/l, all three purinoceptor agonists were active, the potency order being alpha,beta-meATP greater than 2-methylthio ATP = ATP. Preincubation of the slices with tetrodotoxin (TTX) 0.5 mumol/l decreased the spike discharge but did not alter the percent facilitatory effect of alpha,beta-meATP 30 mumol/l. There was no desensitization to alpha,beta-meATP 10 mumol/l on repeated or continuous application. Suramin 100 mumol/l selectively depressed the effect of alpha,beta-meATP 30 mumol/l without interfering with the effect of equiactive concentrations (10-100 mumol/l) of glutamic acid. The concentration-response curve of alpha,beta-meATP was shifted in a parallel manner to the right by suramin 10 mumol/l. While DPCPX 0.1 mumol/l facilitated firing, suramin 100 mumol/l did not change it. In conclusion, LC neurones may possess P2-purinoceptors of an unidentified type, which share some P2x characteristics.