Avtor/Urednik     Čarman-Kržan, Marija; Kržan, Mojca; Schunack, Walter
Naslov     Pharmacological properties of cardiovascular histamine H1 receptor binding sites: characterisation with 2-phenylhistamines
Tip     članek
Vir     Naunyn Schmiedebergs Arch Pharmacol
Vol. in št.     Letnik 355, št. 4
Leto izdaje     1997
Obseg     str. 431-7
ISSN     0028-1298
Jezik     eng
Abstrakt     We determined and compared the molecular properties of histamine H1 receptor binding sites in bovine thoracic aorta smooth muscle and guinea pig myocardial membranes from ventricles with saturation and inhibition binding assay, using 3H-mepyramine to label the receptor and specific and selective H1 receptor agonists of the 2-phenylhistamine group as displacers of specific 3H-mepyramine binding. 3H-mepyramine binds in a saturable manner to a homogenous population of binding sites with a K/D of 5.6 nM and a B/mac of 57 fmol/mg of protein in bovine aorta vascular smooth muscle membranes, whereas in the guinea pig myocardium high and low affinity 3H-mepyramine binding sites exist having the following molecular characteristics: a K/D of 1.6 nM and a B/max of 99 fmol/mg of protein (high affinity site) and a K/D 15.0 nM and a B/max of 466 fmol/mg of protein (low affinity site). Halogenated 2-phenylhistamines: 2-(3-fluor-) (2-FPH), 2-(3-trifluoromethyl-) (2-triFMPH), 2-(3-chloro-) (2-CPH), 2-(3-bromo-) (2-BPH) and 2-(3-iodophenyl) histamine (2-IPH), which showed high selectivity and potency for H1 receptors in the functional pharmacological studies, were potent inhibitors of specific radiologand binding in comparison with histamine and parent nonhalogenated 2-phenylhistamine (2-PH). Their rank order of potencies and affinities differ significantly for the vascular and cardiac H1 receptor binding sites: Specific 3H-mepyramine binding to H1 receptors in bovine vascular smooth muscle membranes was displaced in a biphasic manner by 2-(3-fluor-), 2-(3-trifluoromethyl-), 2-(3-chloro-), 2-(3-bromo-), 2-(3-iodophenyl) histamine and histamine. In guinea pig ventricular myocardium the rank order was 2-(3-iodo-), 2-(3-bromo-), histamine, 2-(3-chloro-), and 2-(3-fluorophenyl) histamine showing better correlation with the lipophilicity of the derivatives than in vasculat tissue (order of lipophilicity: (Abstract truncated at 2000 characters).
Deskriptorji     RECEPTORS, HISTAMINE H1