REGIONAL DIFFERENCES IN ALPHA(1)-ADRENOCEPTOR SUBTYPES AND MECHANISMSIN 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 -(beta-(4-hydroxyphenyl)ethylaminomethyl)tetral one were determined ic the following rabbit arteries: thoracic and abd ominal aorta, mesenteric, renal and iliac arteries, and the alpha(1)-a drenoceptor subtypes mediating contractile mechanisms in vascular smoo th muscle were studied. The pD(2) values for norepinephrine differed c onsiderably 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 whic h there were no stable contractions. In normal PSS, the concentration- response curves for norepinephrine with chloroethylclonidine-pretreatm ent 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 membr ane preparations obtained from chloroethylclonidine-treated strips, th e B-max values (33.2-105.2 fmol/mg protein) for [I-125]HEAT varied con siderably among arteries, while the K-d values(0.20-0.26 nM) were iden tical. The logarithm of B-max values is proportional to the pD(2) valu es for norepinephrine (slope = 0.69, r = 0.961). These observations su ggest thar the regional differences in potency (pD(2) value) of the al pha(1)-adrenoceptor agonist, norepinephrine, are a result of the diffe rences in population and density of alpha(1)-adrenoceptor subtypes in rabbit arteries. (C) 1998 Elsevier Science B.V. All rights reserved.