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.
Allen
M C
MC
Department of Pharmacy, University of Brighton, UK.
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D017442:Histamine Agonists / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology*; D006822:Hybrid Cells; D007093:Imidazoles / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D017442:Histamine Agonists; D006633:Histamine Antagonists; D007093:Imidazoles; D007473:Ion Channels; D010880:Piperidines; D018100:Receptors, Histamine H3; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D007550:Isothiuronium; C077791:iodophenpropit; C077430:imetit; D013890:Thiourea; C052075:thioperamide