Characterization of coexistent histamine H1- and H2-receptor binding sites in the purified guinea pig myocardial membranes from ventricles (original) (raw)
Related papers
Histamine receptors in the heart—Molecular characteristics, physiology and pharmacology
Inflammopharmacology, 1996
Histamine is a normal constituent of mammalian heart. It affects cardiac function mainly through stimulating histamine H 1-and H2-receptor subtypes. The simultaneous activation of HI-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. HI-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 intracelhilar signaling, 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 (KD 0.4 nmol/L and Bmax 100 fmol/mg of protein) and a lowaffinity (KD 4.5 nmol/L, Bm~ 466 fmol/mg of protein) HI-receptor-binding site and only a single population of less-abundant high-affinity H2-receptor binding sites (KD 1.0 nmol/L and Bm,~ 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.
Histamine H 1 -Receptor in Heart: Unique Electrophoretic Mobility and Autoradiographic Localization
Journal of Neurochemistry, 1990
Histamine Hi-receptors, visualized in the guinea pig heart by autoradiography using [ i251]iodobolpyramine as a specific probe, are abundant in the nodal tissue and cardiac vessels but also occur heterogeneously in the myocardium. Following photoaffinity labeling with ['251]iodoazidophenpyramine and electrophoresis, the ligand binding domain of the heart H,-receptor was shown to be present on a major 68-kDa and a less abundant 54-to 58-kDa protein. The 68-kDa protein displayed a molecular size higher in heart than in all other tissues (56 kDa). This indicates the existence of at least two isoforms of the HI-receptor; the cardiac isoform, however, was pharmacologically indistinguishable from the common isoform studied in cerebellar membranes using available ligands. Its distinct electrophoretic properties suggest that the cardiac isoform may have a unique function. Key Words: Photoaffinity labeling-Electrophoretic analysis-Autoradiographic localization-['251]Iodobolpyramine-['Z51]Iodoazidophenpyramine. Ruat M. et al. Histamine HIreceptor in heart: Unique electrophoretic mobility and autoradiographic localization. J. Neurochem. 55, 379-385 ( 1 990). ~ ~~ ~ ~~~
Journal of Pharmacology and Experimental Therapeutics, 2007
Previous studies revealed pharmacological differences between human and guinea pig histamine H 2 receptors (H 2 Rs) with respect to the interaction with guanidine-type agonists. Because H 2 R species variants are structurally very similar, comparative studies are suited to relate different properties of H 2 R species isoforms to few molecular determinants. Therefore, we systematically compared H 2 Rs of human (h), guinea pig (gp), rat (r), and canine (c). Fusion proteins of hH 2 R, gpH 2 R, rH 2 R, and cH 2 R, respectively, and the short splice variant of G s␣ , G s␣S , were expressed in Sf9 insect cells. In the membrane steady-state GTPase activity assay, cH 2 R-G s␣S but neither gpH 2 R-G s␣S nor rH 2 R-G s␣S showed the hallmarks of increased constitutive activity compared with hH 2 R-G s␣S , i.e., increased efficacies of partial agonists, increased potencies of agonists This work was supported by the Research Training Program (Graduiertenkolleg) GRK 760 "Medicinal Chemistry: Molecular Recognition-Ligand-Receptor Interactions" of the Deutsche Forschungsgemeinschaft.
Biochimica et Biophysica Acta (BBA) - General Subjects, 1979
In particulate preparations from guinea-pig ventricle, histamine in the concentration range 10-6--10 -3 M caused a 3--5-fold stimulation of adenylate cyclase activity which was dependent on the presence of GTP. The effects of fourteen analogs of histamine were examined on this cyclase preparation. Five of the compounds studied proved to be partial agonists relative to histamine while nine others had essentially the same intrinsic activity as histamine. The intrinsic activities of the partial agonists were increased by GppNHp to the extent that dimaprit, which was a partial agonist in the presence of GTP, became a full agonist in the presence of GppNHp. The relative potencies of the full agonists as activators of the cyclase were found to correlate with the relative potencies on physiologically defined H2 receptor systems. Activation of the cyclase by histamine, as well as by several of the agonist analogs, including dimaprit and tolazoline, was completely blocked by the H2 antagonist cimetidine, but was not affected by pharmacologically relevant concentrations of the H~ antagonist mepyramine, the ~-blocker alprenolol, or the s-blocker phentolamine. The results suggest that all the agonists studied probably interact with a common H2 receptor site on the cardiac muscle cell leading to activation of Abbreviation: GppNHp, guanosine-5-(~,7-imino)triphosphate. 156 adenylate cyclase. The accompanying increase in cyclic AMP is presumably responsible for the chronotropic and inotropic effects of histamine and related compounds on cardiac muscle.
British Journal of Pharmacology, 2006
1 Various histamine derivatives were investigated at the human H 3 receptor (H 3 R) and H 4 receptor (H 4 R) stably expressed in human embryonic kidney (HEK)-293 cells using [ 125 I]iodoproxyfan and [ 3 H]histamine binding, respectively. 2 In Tris buffer, [ 3 H]histamine binding to membranes of HEK(hH 4 R) cells was monophasic (K D of 3.870.8 nM). In phosphate buffer, the Hill coefficient was decreased (n H ¼ 0.570.1) and a large fraction of the binding was converted into a low-affinity component (K D ¼ 67727 nM).
Correlation of histamine H1 receptor function and [3H]mepyramine binding in porcine tracheal tissue
European Journal of Pharmacology, 1987
In order to validate the use of [3H]mepyramine as a radioligand to label airway histamine H a receptors, the results of radioligand binding experiments using porcine tracheal tissue membranes were compared with the results of physiologic studies measuring histamine-induced trachealis muscle contraction. Close agreement was found between histamine-induced [3H]mepyramine binding inhibition and histamine concentration-contraction-response curves. Close agreement was also found between the K D of mepyramine-induced [3H]mepyramine binding inhibition and the KO of mepyramine antagonism of muscle contractions stimulated by 10-4 M histamine. [3H]Mepyramine binding was found to be rapid, reversible, saturable and stereospecific. Only H a agonists and antagonists displayed potent [3H]mepyramine binding inhibition in competition binding studies. The results fulfill criteria for histamine H a receptor identification by radioligand binding with [3H]mepyramine.