DIFFERENCES IN THE MODE OF STIMULATION OF CULTURED RAT SYMPATHETIC NEURONS BETWEEN ATP AND UDP

Postganglionic sympathetic neurons possess at least two excitatory rec eptors for nucleotides: P2X-purinoceptors and separate receptors for u racil nucleotides.(2,3,5,6,9,12) In cultured neurons from rat superior cervical ganglia (SCG), both receptors, when activated, induce releas e of noradrenaline.(2,3) Here we describe marked differences between t he responses of cultured neurons from rat thoracolumbal paravertebral ganglia to ATP and UDP. ATP elicited release of previously taken up [H -3]noradrenaline, induced an inward current, and increased the intra-a xonal free calcium level, over the same range of micromolar concentrat ions. UDP was more potent than ATP in releasing [H-3]noradrenaline but induced an inward current only at a concentration of 1 mM and caused much smaller increases in intraaxonal free calcium. The mechanism of a ction of ATP presumably consists of P2X-purinoceptor(4,22) activation followed by depolarization, calcium entry through voltage-sensitive ch annels and exocytosis. The mode of action of UDP is different. It prob ably activates a G-protein-coupled pyrimidinoceptor. The pyrimidinocep tor(19,24,25) then possibly mediates mobilization of intracellular cal cium close to the sites of transmitter release and in addition an incr ease in the calcium sensitivity of the exocytotic apparatus. (C) 1997 IBRO. Published by Elsevier Science Ltd.