Pharmacological properties of alpha-mangostin, a novel histamine H1 receptor antagonist.
In the isolated rabbit thoracic aorta and guinea-pig trachea, alpha-mangostin inhibited histamine-induced contractions in a concentration-dependent manner in the presence or absence of cimetidine, a histamine H2 receptor antagonist. But KCl-, phenylephrine- or carbachol-induced contractions were not affected by alpha-mangostin. The concentration-contractile response curve for histamine was shifted to the right in a parallel manner by alpha-mangostin. In the presence of chlorpheniramine, a histamine H1 receptor antagonist, alpha-mangostin did not affect the relaxation of the rabbit aorta induced by histamine. In the guinea-pig trachea, alpha-mangostin had no effect on the relaxation induced by dimaprit, a histamine H2 receptor agonist. alpha-Mangostin caused a concentration-dependent inhibition of the binding of [3H]mepyramine, a specific histamine H1 receptor antagonist to rat aortic smooth muscle cells. Kinetic analysis of [3H]mepyramine binding indicated the competitive inhibition by alpha-mangostin. These results suggest that alpha-mangostin is a novel competitive histamine H1 receptor antagonist in smooth muscle cells.
Chairungsrilerd
N
N
Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Furukawa
K
K
Ohta
T
T
Nozoe
S
S
Ohizumi
Y
Y
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D016015:Logistic Models; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D011738:Pyrilamine / Q000378:metabolism; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011970:Receptors, Histamine H2 / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014966:Xanthenes / Q000494:pharmacology*; D044004:Xanthones
D006634:Histamine H1 Antagonists; D011970:Receptors, Histamine H2; D014966:Xanthenes; D044004:Xanthones; D011738:Pyrilamine; C021053:mangostin