HISTAMINE H-3 RECEPTORS MODULATE THE RELEASE OF [H-3] ACETYLCHOLINE FROM SLICES OF RAT ENTORHINAL CORTEX - EVIDENCE FOR THE POSSIBLE EXISTENCE OF H-3 RECEPTOR SUBTYPES

1 The effect of agents which interact with the histamine H-3 receptor on potassium-stimulated tritium release from slices of rat entorhinal cortex preloaded with [H-3]-choline is described. We have examined the effects of the selective H-3 receptor agonist, (R)-alpha-methylhistamine (RAMH), and a number of H-3 receptor antagonists, including the selective compound thioperamide, on the potassium-stimulated release of tritium. 2 In the presence of mepyramine and ranitidine, RAMH (0.01 - 10 muM) inhibited potassium-stimulated tritium release in a concentration-dependent manner, EC50 = 0.11 muM. The maximum inhibition was approximately 50%. 3 Thioperamide displaced the RAMH concentration-response curve to the right yielding a pK(B) value of 8.4. There was no change in the maximum response to RAMH. 4 Other H-3 receptor antagonists, including impromidine and burimamide, also caused rightwards displacement of the linear portion of the RAMH concentration-response curve. However, phenyl-butanoylhistamine and betahistine, which are reported to be relatively potent H-3 receptor antagonists, showed very low affinity. 5 Thioperamide (0.001-1 muM) alone enhanced the potassium-stimulated release of tritium in a concentration-dependent manner. Maximum effects were observed at 0.1 - 1 muM thioperamide, enhancing release by approximately 20%. 6 Results are discussed in terms of the regulatory role of H-3 receptors on acetylcholine release and the possible existence of H-3 receptor subtypes.