CULTURED CHICK SYMPATHETIC NEURONS - PROSTANOID EP(1) RECEPTOR-MEDIATED FACILITATION OF NORADRENALINE RELEASE

Prostanoid EP receptor-mediated modulation of noradrenaline release fr om cultured chick sympathetic neurons was investigated. Transmitter re lease from dissociated cell cultures of embryonic paravertebral gangli a, loaded with [H-3]-noradrenaline, was elicited either by electrical field stimulation (36 pulses/3 Hz) or by elevating the extracellular c oncentration of K+ (to 30 mM; for 2 min). Prostaglandin E(2) (PGE(2); 0.01-3 mu M) enhanced electrically evoked [H-3]-noradrenaline release in a concentration-dependent manner with a maximal increase by about 5 0% at 1 mu M. Also iloprost (0.1-3 mu M) increased transmitter release concentration-dependently, whereas misoprostol (0.1-3 mu M) had no ef fect. Indometacin (10 mu M) influenced neither evoked release per se n or the enhancement caused by PGE(2). AH6809 (3 mu M), a selective EP(1 ) receptor antagonist, blocked the enhancement caused by both PGE(2) a nd iloprost. K+-evoked noradrenaline release, which was virtually inse nsitive to tetrodotoxin (0.3 mu M), was increased by PGE(2) to an exte nt comparable to that observed after electrical stimulation. In summar y, the present data indicate that PGE(2) facilitates noradrenaline rel ease from cultured chick sympathetic neurons by a receptor which shows the pharmacological profile of the EP(1) subtype and is probably loca ted at the processes of the neuron.