Histamine H3 receptors modulate the release of [3H]‐acetylcholine from slices of rat entorhinal cortex: evidence for the possible existence of H3 receptor subtypes

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Abstract
1 The effect of agents which interact with the histamine H3 receptor on potassium-stimulated tritium release from slices of rat entorhinal cortex preloaded with [3H]-choline is described. We have examined the effects of the selective H3 receptor agonist, (R)-α-methylhistamine (RAMH), and a number of H3 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 μm) inhibited potassium-stimulated tritium release in a concentration-dependent manner, EC50 = 0.11 μm. The maximum inhibition was approximately 50%. 3 Thioperamide displaced the RAMH concentration-response curve to the right yielding a pKB value of 8.4. There was no change in the maximum response to RAMH. 4 Other H3 receptor antagonists, including impromidine and burimamide, also caused rightwards displacement of the linear portion of the RAMH concentration-response curve. However, phenylbutanoylhistamine and betahistine, which are reported to be relatively potent H3 receptor antagonists, showed very low affinity. 5 Thioperamide (0.001–1 μm) alone enhanced the potassium-stimulated release of tritium in a concentration-dependent manner. Maximum effects were observed at 0.1–1 μm thioperamide, enhancing release by approximately 20%. 6 Results are discussed in terms of the regulatory role of H3 receptors on acetylcholine release and the possible existence of H3 receptor subtypes.