Regional differences in α1-adrenoceptor subtypes and mechanisms in rabbit arteries

Abstract

Contractility mediated through α 1-adrenoceptor subtypes and the maximum binding site ( B max value) and the dissociation constant ( K d value) for [ 125 I] ]HEAT ( [ 125 I] iodo-2-( β-(4-hydroxyphenyl)ethylaminomethyl)tetralone) were determined in the following rabbit arteries: thoracic and abdominal aorta, mesenteric, renal and iliac arteries, and the α 1-adrenoceptor subtypes mediating contractile mechanisms in vascular smooth muscle were studied. The p D 2 values for norepinephrine differed considerably among the arteries in the presence of nicardipine (10 −5 M), while the p A 2 values for 5-methylurapidil against norepinephrine were identical at low affinity in all the arteries used. In Ca 2+-free physiological saline solution (Ca 2+-free PSS), the p A 2 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 (p D 2 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 [ 125 I] HEAT binding study using membrane preparations obtained from chloroethylclonidine-treated strips, the B max values (33.2–105.2 fmol/mg protein) for [ 125 I] HEAT varied considerably among arteries, while the K d values (0.20–0.26 nM) were identical. The logarithm of B max values is proportional to the p D 2 values for norepinephrine (slope=0.69, r=0.961). These observations suggest that the regional differences in potency (p D 2 value) of the α 1-adrenoceptor agonist, norepinephrine, are a result of the differences in population and density of α 1-adrenoceptor subtypes in rabbit arteries.