title: Inhibitory effects of amiloride on alpha adrenoceptors in canine vascular smooth muscle.
abstract: Amiloride inhibits vascular smooth muscle contractions from canine aorta and saphenous vein. The mechanisms were studied using radioligand binding and functional techniques. Amiloride inhibited [3H]prazosin and [3H]rauwolscine binding to alpha-1 and alpha-2 adrenoceptors in a concentration-dependent manner. Amiloride increased Kd values for [3H]rauwolscine without affecting the maximum binding of [3H]prazosin. These results suggest that the drug interacts with the alpha-1 adrenoceptor binding sites in a competitive manner and with the alpha-2 adrenoceptor binding sites in a noncompetitive manner. Amiloride reduced maximal contractile responses to agonists selective for both alpha adrenoceptors and to elevated K+, the EC50 values were increased by about 10-fold in the presence of amiloride. In Ca+(+)-free Krebs' solution, contractions induced in saphenous vein after addition of Ca++ in saphenous vein in the presence of adrenoceptor agonists were inhibited by amiloride. Our results suggest that amiloride reduced alpha-1 and alpha-2 adrenoceptor-mediated responses and inhibited Ca++ influx.
authors.affiliation: Department of Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: A G
authors.initials: AG
authors.lastname: Shi
authors.forename: Z L
authors.initials: ZL
authors.lastname: Wang
authors.forename: C Y
authors.initials: CY
authors.lastname: Kwan
authors.forename: E E
authors.initials: EE
authors.lastname: Daniel
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002478:Cells, Cultured; D004285:Dogs; D005260:Female; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000378:metabolism; D011224:Prazosin / Q000037:antagonists & inhibitors / Q000378:metabolism; D011869:Radioligand Assay; D014316:Tritium; D014661:Vasoconstriction / Q000187:drug effects; D015016:Yohimbine / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D014316:Tritium; D010656:Phenylephrine; D015016:Yohimbine; D000584:Amiloride; D009638:Norepinephrine; D011224:Prazosin