title: Beta adrenoceptors in the canine large coronary arteries: beta-1 adrenoceptors predominate in vasodilation.
abstract: Beta adrenoceptors of the canine large coronary artery were characterized by observing the effects of the subtype selective antagonists, metoprolol (beta-1) and ICI 118,551 (beta-2), on the vasodilator responses of isolated and perfused preparations to beta adrenoceptor agonists and in the radioligand binding assay. The integrity of the endothelium was checked by acetylcholine-induced vasodilations. Without any precontraction, isoproterenol, norepinephrine, epinephrine and procaterol (selective beta-2 agonist) dilated the canine large coronary artery pretreated with phentolamine (10(-5) M). The rank order of agonist potency was isoproterenol greater than norepinephrine greater than epinephrine greater than procaterol. The pA2 values for metoprolol and ICI 118,551 were determined by the antagonisms of the vasodilator responses to isoproterenol and procaterol. The slopes of Schild plots for metoprolol and ICI 118,551 against isoproterenol and the value for ICI 118,551 against procaterol were not significantly different from unity, but the value for metoprolol against procaterol was significantly less than unity. The pA2 value for metoprolol against isoproterenol was 7.48 and those values for ICI 118,551 against isoproterenol and procaterol was 7.19 and 7.25, respectively. These pA2 values are typical for beta-1 adrenoceptors. The beta adrenoceptors of the canine large coronary artery were examined further using an antagonist [125I]iodocyanopindolol as a ligand for the binding of beta adrenoceptors. The [125I]iodocyanopindolol binding to the canine coronary artery smooth muscle membrane was saturable with a KD of 63.7 pM and a total number of radioligand binding sites of 44 fmol/mg of protein.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D020120:Iodocyanopindolol; D010869:Pindolol; D008790:Metoprolol