Regional differences in alpha1-adrenoceptor subtypes and mechanisms in rabbit arteries.
Contractility mediated through alpha1-adrenoceptor subtypes and the maximum binding site (Bmax value) and the dissociation constant (Kd value) for [125I]HEAT ([125I]iodo-2-(beta-(4-hydroxyphenyl)ethylaminomethyl)tetralone) were determined in the following rabbit arteries: thoracic and abdominal aorta, mesenteric, renal and iliac arteries, and the alpha1-adrenoceptor subtypes mediating contractile mechanisms in vascular smooth muscle were studied. The pD2 values for norepinephrine differed considerably among the arteries in the presence of nicardipine (10(-5) M), while the pA2 values for 5-methylurapidil against norepinephrine were identical at low affinity in all the arteries used. In Ca2+-free physiological saline solution (Ca2+-free PSS), the pA2 values for 5-methylurapidil were also similar except for the renal artery, in which there were no stable contractions. In normal PSS, the concentration-response curves for norepinephrine with chloroethylclonidine-pretreatment were shifted to the right (pD2 values of 5.58, 5.70, 5.74, 5.98 and 6.38 for thoracic and abdominal aorta, mesenteric, renal and iliac arteries, respectively). In the [125I]HEAT binding study using membrane preparations obtained from chloroethylclonidine-treated strips, the Bmax values (33.2-105.2 fmol/mg protein) for [125I]HEAT varied considerably among arteries, while the Kd values (0.20-0.26 nM) were identical. The logarithm of Bmax values is proportional to the pD2 values for norepinephrine (slope=0.69, r=0.961). These observations suggest that the regional differences in potency (pD2 value) of the alpha1-adrenoceptor agonist, norepinephrine, are a result of the differences in population and density of alpha1-adrenoceptor subtypes in rabbit arteries.
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi, Chiba, Japan.
M
M
Satoh
K
K
Enomoto
H
H
Niwano
H
H
Fujimura
Y
Y
Toyama
I
I
Takayanagi
K
K
Koike
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010627:Phenethylamines / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000502:physiology*; D044024:Tetralones; D014018:Tissue Distribution
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010627:Phenethylamines; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D044024:Tetralones; C057446:5-methylurapidil; C010652:BE 2254; D009638:Norepinephrine