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Histamine H 3 receptors modulate the release of [ 3 H]‐acetylcholine from slices of rat entorhinal cortex: evidence for the possible existence of H 3 receptor subtypes
Author(s) -
Clapham J.,
Kilpatrick G.J.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb13386.x
Subject(s) - thioperamide , histamine h3 receptor , chemistry , mepyramine , endocrinology , medicine , agonist , histamine , muscarinic acetylcholine receptor , receptor , histamine receptor , acetylcholine , biochemistry , biology , antagonist
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 [ 3 H]‐choline is described. We have examined the effects of the selective H 3 receptor agonist, (R)‐α‐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 μ m ) inhibited potassium‐stimulated tritium release in a concentration‐dependent manner, EC 50 = 0.11 μ m . The maximum inhibition was approximately 50%. 3 Thioperamide displaced the RAMH concentration‐response curve to the right yielding a p K 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, phenylbutanoylhistamine and betahistine, which are reported to be relatively potent H 3 receptor antagonists, showed very low affinity. 5 Thioperamide (0.001–1 μ m ) alone enhanced the potassium‐stimulated release of tritium in a concentration‐dependent manner. Maximum effects were observed at 0.1–1 μ m 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.