BINDING CHARACTERISTICS OF A HISTAMINE H-3 RECEPTOR ANTAGONIST, [H-3] S-METHYLTHIOPERAMIDE - COMPARISON WITH [H-3] (R)ALPHA-METHYLHISTAMINE BINDING TO RAT-TISSUES

The release and synthesis of neuronal histamine are regulated by histaminergic autoreceptors named as histamine H-3 receptors. The development of radiolabeled histamine H-3 antagonists is needed to characterize the binding of antagonists to these receptors. Here we describe the binding characteristics of a new histamine H-3-receptor antagonist, [H-3]S-methylthioperamide (SMT), to rat tissues, and compare its binding with that of [H-3](R)alpha-methylhistamine ((R)alpha MH), a selective histamine H-3-receptor agonist. The binding of [H-3]SMT to the membranes of rat forebrain was found to be stereoselective, saturable, reversible and temperature-dependent. Saturation binding experiments indicated a single class of high affinity sites for [H-3]SMT in forebrain membranes (K-D=2.1 nM, B-max=24.3 pmol/g of tissue at 4 degrees C). The B-max was approximately 3 times that of [H-3](R)alpha MH binding to rat forebrain membranes (K-D=2.5 nM, B-max=7.3 pmol/g of tissue at 25 degrees C). Autoradiographic images of [H-3]SMT binding in the brain were essentially the same as those of [H-3](R)alpha MH. [H-3]SMT also bound appreciably to peripheral tissues (the liver, adrenal, stomach, ileum, kidney, lung and bladder), whereas the [H-3](R)alpha MH bindings to these peripheral tissues were negligible. These results indicate that [H-3]SMT binds to H-3 receptors primarily in the central nervous system, and that it also has high affinity toward non-H-3 receptors, probably hemoproteins, in peripheral tissues.