Differences in the mode of stimulation of cultured rat sympathetic neurons between ATP and UDP.

Postganglionic sympathetic neurons possess at least two excitatory receptors for nucleotides: P2X-purinoceptors and separate receptors for uracil nucleotides. In cultured neurons from rat superior cervical ganglia (SCG), both receptors, when activated, induce release of noradrenaline. Here we describe marked differences between the responses of cultured neurons from rat thoracolumbal paravertebral ganglia to ATP and UDP. ATP elicited release of previously taken up [3H]noradrenaline, induced an inward current, and increased the intra-axonal free calcium level, over the same range of micromolar concentrations. UDP was more potent than ATP in releasing [3H]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 action of ATP presumably consists of P2X-purinoceptor activation followed by depolarization, calcium entry through voltage-sensitive channels and exocytosis. The mode of action of UDP is different. It probably activates a G-protein-coupled pyrimidinoceptor. The pyrimidinoceptor then possibly mediates mobilization of intracellular calcium close to the sites of transmitter release and in addition an increase in the calcium sensitivity of the exocytotic apparatus.