Histamine receptors in the heart—Molecular characteristics, physiology and pharmacology

Abstract

Histamine is a normal constituent of mammalian heart. It affects cardiac function mainly through stimulating histamine H1- and H2-receptor subtypes. The simultaneous activation of H1- and H2-receptors in the heart results in: a positive inotropic and chronotropic effect, a negative dromotropic effect, increased automaticity and increased coronary blood flow. H1- and H2-receptors have already been cloned from different, but not yet from cardiac, tissue. They are two independent molecular entities differing in the length of their amino acid sequence, pathways of transmembrane and intracellular signalling, characteristics of their binding sites and selectivity for the specific agonists and/or antagonists. Our results of radioligand binding studies show the presence in the heart of a high-affinity (K D 0.4 nmol/L andB max 100 fmol/mg of protein) and a low-affinity (K D 4.5 nmol/L,B max 466 fmol/mg of protein) H1-receptor-binding site and only a single population of less-abundant high-affinity H2-receptor binding sites (K D 1.0 nmol/L andB max 27 fmol/mg of protein). The role of the histamine in cardiac pathophysiology is well established but the physiological role is unclear. The only proposed physiological role of histamine in the heart is the modulation of noradrenaline release from sympathetic nerve terminals, where H3-receptor subtypes might be involved.