CORELEASE OF NORADRENALINE AND ATP FROM SYMPATHETIC NEURONS CULTURED

The vesicles of postganglionic sympathetic axons store both noradrenal ine and ATP.(22,31) The theory of noradrenaline-ATP co-transmission im plies that both compounds are released by nerve action potentials and elicit postjunctional effects. Many properties of postjunctional respo nses support the theory.(3,12,22,27) However, neural release of ATP ha s been difficult to detect biochemically:(22,31) by far the major part of the overflow of ATP from intact tissues upon sympathetic nerve sti mulation(13-15,23,26,30) comes from non-neural elements, especially sm ooth muscle and endothelial cells.(5,17,19,20,28,30) Here we describe a parallel electrically evoked overflow of [H-3]noradrenaline and endo genous ATP from cultured chick sympathetic neurons. The overflow was a bolished by tetrodotoxin, omega-conotoxin and withdrawal of Ca2+, was increased by tetraethylammonium and 4-aminopyridine, and was not chang ed by prazosin or suramin. The results demonstrate directly the action potential-evoked, Ca2+-dependent and presumably vesicular and exocyto tic release of ATP from postganglionic sympathetic neurons. They suppo rt the co-transmitter theory and suggest that cultured sympathetic neu rons are a preparation in which noradrenaline-ATP co-release can be ex amined free from postjunctional components.