Analysis of α 1-adrenoceptor subtypes in rabbit aorta and arteries: regional difference and co-existence

Abstract

This study was done to determine the α 1-adrenoceptor subtypes and to characterize the functional role of α 1D-adrenoceptors in the following rabbit arteries: thoracic and abdominal aorta, mesenteric, renal and iliac arteries. In all arteries, selective α 1D-adrenoceptor antagonist BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspirol(4,5) decane-7,9-dione dihydrochloride) dose dependently shifted the concentration–response curves for norepinephrine to the right. Schild plots of the results obtained from the inhibition by BMY 7378 for norepinephrine yielded a straight line with a slope of unity in thoracic ( pA 2 6.54±0.02) and abdominal ( pA 2 6.73±0.03) aorta. Slopes of Schild plots obtained from the inhibition by BMY 7378 for norepinephrine were significantly different from unity in mesenteric, renal and iliac arteries. Slopes of Schild plots for BMY 7378 were not different from unity in chloroethylclonidine-treated thoracic ( pA 2 6.49±0.14) and abdominal ( pA 2 6.61±0.11) aorta. Slopes of Schild plots for BMY 7378 were significantly different from unity in chloroethylclonidine-treated mesenteric, renal and iliac arteries. On the other hand, in Ca 2+-free physiological saline solution (Ca 2+-free PSS) slopes obtained from Schild plots for BMY 7378 were not different from unity in thoracic ( pA 2 6.41±0.09) and abdominal ( pA 2 6.28±0.07) aorta and mesenteric ( pA 2 6.55±0.06), renal ( pA 2 6.24±0.10) and iliac ( pA 2 6.64±0.13) arteries. BMY 7378 inhibited [ 3 H ]prazosin binding to thoracic (p K i 6.44±0.08) and abdominal (p K i 6.59±0.02) aorta with low potency, and mesenteric (p K i High 8.66±0.28, p K i Low 6.34±0.14), renal (p K i High 8.71±0.33, p K i Low 6.45±0.03) and iliac artery (p K i High 8.60±0.24, p K i Low 6.56±0.13). These results suggest that α 1D-adrenoceptors play a significant role for contractile responses in renal and iliac artery, but play virtually no role in thoracic and abdominal aorta and that an α 1-adrenoceptor subtype, which is pharmacologically distinguishable from the α 1A-, α 1B- and α 1D-adrenoceptor subtype, may co-exist in mesenteric artery.