Differences of antagonism for a selective alpha1D-adrenoceptor antagonist BMY 7378 in the rabbit thoracic aorta and iliac artery.
Based on the affinity of alpha1D adrenoceptor subtype for a selective antagonist BMY 7378, we studied its functional role in rabbit thoracic aorta and iliac artery, and evaluated the subtypes of the alpha1-adrenoceptors that are activated by phenylephrine (a full agonist) and tizanidine (a partial agonist). In thoracic aorta, the concentration response curves of phenylephrine and tizanidine were antagonized by BMY 7378 with low potency (pA2 values 6.68+/-0.06 and 6.67+/-0.06, slopes of Schild plot 1.06+/-0.04 and 1.01+/-0.04, respectively). On the other hand, in iliac artery concentration response curves for phenylephrine were potently antagonized by a low concentration of BMY 7378, and the slope (0.75+/-0.02) of the Schild plot was significantly different from unity. In iliac artery, a concentration response curve of tizanidine was antagonized by BMY 7378 with low potency (pA2 value 6.64+/-0.08, slope of Schild plot 1.01+/-0.05). These results suggest that an alpha1D-adrenoceptor subtype contributes to alpha1-adrenoceptor mediating muscle contraction in iliac artery, but not in thoracic aorta of rabbit, and that it is activated by a full agonist phenylephrine but not by a partial agonist tizanidine.
Satoh
M
M
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Enomoto
K
K
Takayanagi
I
I
Koike
K
K
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D007083:Iliac Artery / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011817:Rabbits; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; C053428:BMY 7378