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

Contractility mediated through alpha(1)-adrenoceptor subtypes and the maximum binding site (B-max value) and the dissociation constant (K-d value) for [I-125]HEAT ([I-125]iodo-2-(beta-(4-hydroxyphenyl)ethylaminomethyl)tetralone were determined ic the following rabbit arteries: thoracic and abdominal aorta, mesenteric, renal and iliac arteries, and the alpha(1)-adrenoceptor subtypes mediating contractile mechanisms in vascular smooth muscle were studied. The pD(2) values for norepinephrine differed considerably among the arteries in the presence of nicardipine (10(-5) M), while the pA(2) 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 pA(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 (pD(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 [I-125]HEAT binding study using membrane preparations obtained from chloroethylclonidine-treated strips, the B-max values (33.2-105.2 fmol/mg protein) for [I-125]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 pD(2) values for norepinephrine (slope = 0.69, r = 0.961). These observations suggest thar the regional differences in potency (pD(2) value) of the alpha(1)-adrenoceptor agonist, norepinephrine, are a result of the differences in population and density of alpha(1)-adrenoceptor subtypes in rabbit arteries. (C) 1998 Elsevier Science B.V. All rights reserved.