POSSIBLE PARTICIPATION OF HISTAMINE H-3 RECEPTORS IN THE MODULATION OF NORADRENALINE RELEASE FROM RAT SPINAL-CORD SLICES

Rat spinal cord slices prelabelled with [H-3]noradrenaline were superf used with a medium containing 1 mu M desipramine plus 0.3 mu M phentol amine. Histamine (0.01-10 mu M) and the selective histamine H-3 recept or agonist R-(-)-alpha-methylhistamine (0.001-10 mu M) caused a concen tration-dependent decrease in the release of radioactivity evoked by e lectrical field stimulation (0.8 Hz, 20 mA, 2 min). The inhibitory eff ect of histamine was not modified by either pyrilamine (1 mu M) or ran itidine (10 mu M), but it was antagonized by burimamide (1 mu M). The inhibitory action of histamine (1 mu M) was attenuated by pertussis to xin (3 mu g/ml) and was abolished by N-ethylmaleimide (30 mu M). Neith er forskolin (10 mu M) nor rolipram (100 mu M), nor the combination of both drugs, modified the inhibitory effect of histamine. Histamine (1 mu M) did not modify the overflow of tritium induced by electrical st imulation in the absence of phentolamine. The present results suggest that in the rat spinal cord the release of noradrenaline elicited by e lectrical stimulation is negatively modulated by histamine, probably t hrough the activation of histamine H-3 receptors. This modulatory mech anism is likely to involve the participation of regulatory G(0)/G(1) p roteins.