Agonist and antagonist effects of histamine H3 receptor ligands on 5-HT3 receptor-mediated ion currents in NG108-15 cells.

The ability of histamine H3 receptor ligands to interact with 5-HT3 receptors in NG108-15 cells was studied using the whole cell patch clamp recording technique. Imetit, a histamine H3 receptor agonist, generated inward currents and exhibited weak partial agonist activity at the 5-HT3 receptor (EC50 = 11.8 microM). Imetit-induced currents were slow to desensitize and at a high concentration reduced in size. The histamine H3 receptor antagonists iodophenpropit and thioperamide did not generate inward currents but were able to inhibit 5-hydroxytryptamine (5-HT) responses with an IC50 of 1.57+/-0.3 microM and 13.7+/-3.5 microM, respectively. Thioperamide is probably a non-competitive antagonist which may have more than one binding site on the receptor.