Characterization of histamine H2-like receptors in duck cerebral cortical membranes by [3H]tiotidine binding

A selective (according to mammalian criteria) histamine (HA) H-2-receptor radioligand [H-3]tiotidine ([H-3]TIOT) was used to characterize HA receptors in duck cerebral cortex by an in vitro binding technique. The specific binding of [H-3]TIOT to duck cerebral cortical membranes was found to be rapid, stable, saturable, reversible, and of high affinity. Saturation analysis resulted in a linear Scatchard plot suggesting binding to a single class of receptor binding sites with high affinity (K-d = 19.5 nM) and high capacity (B-max = 356 fmol/mg protein). Competition studies showed the following relative rank order of potency of various HA receptor ligands to inhibit the [H-3]TIOT binding: antagonists, tiotidine much greater than ranitidine approximate to zolantidine greater than or equal to cimetidine much greater than mepyramine > thioperamide; agonists, HA greater than or equal to 4-methylHA > 2-methylHA > dimaprit much greater than Ralpha-methylHA. The biphasic nature of the displacement curve for HA and the effect of 5'-guanylimidodiphosphate indicate the coupling of the studied receptor to G-protein. It is suggested that HA receptors in the duck cerebral cortex labelled with [H-3]TIOT represent either avian-specific H-2-like HA receptors or a novel subtype of HA receptors, coupled to a signalling pathway other than the adenylyl cyclase/cyclic adenosine monophosphate one. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.