Regulation of the postsynaptic alpha-adrenergic receptor in rat mesenteric artery. Effects of chemical sympathectomy and epinephrine treatment.

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Abstract
Vascular smooth muscle sensitivity to catecholamine-induced contraction is increased after catecholamine depletion by chemical sympathectomy and decreased after exogenous catecholamine administration. To investigate the role of the vascular .alpha.-adrenergic receptor in these alterations, the .alpha.-1 selective radioligand, (3H)-WB-4101, [phenoxy-3-3H(N)]-(2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane was used to characterize the vascular postsynaptic .alpha.-adrenergic receptor in a membrane-rich particulate fraction of the rat mesenteric artery. Binding of (3H)-WB-4101 was rapid, readily reversible, stereospecific, and saturable. Scatchard analysis described a single class of binding sites with Kd of 0.76 .+-. 0.15 nM and a maximal binding capacity (Bmax) of 99 .+-. 13 f[femto]mol/mg protein. .alpha.-Adrenergic agonists competed for the (3H)-WB-4101 binding site in the .alpha.-adrenergic potency order of (-)-epinephrine (Kd = 3.0 .mu.M) > (-)-norepinephrine (Kd = 8.8 .mu.M) > (-)-isoproterenol (Kd = 57 .mu.M) and the .alpha.-adrenergic antagonist phentolamine (Kd = 7.6 nM) was 1000 times more potent than the .beta.-adrenergic antagonist, (.+-.)-propranolol (Kd = 7400 nM). The number and affinity of .alpha.-adrenergic binding sites were studied in hyper- and hypo-adrenergic states. In mesenteric arteries from rats treated with exogenous epinephrine for 4 days, Bmax was decreased to 53 .+-. 10 fmol/mg protein (n = 4, P < 0.01) but Kd for (3H)-WB-4101 was unchanged. In mesenteric arteries from rats depleted of catecholamines with reserpine, Bmax was unchanged (96 .+-. 15 fmol/mg protein) but Kd for (3H)-WB-4101 was decreased to 0.34 .+-. 0.07 nM (n = 6, P < 0.01) and Kd for (-)-epinephrine was decreased to 0.40 .+-. 0.19 .mu.M (n = 6, P < 0.01). The effect of reserpine treatment was time dependent, being evident within 1 h and reaching a maximum after 3-7 days. The effects of catecholamine depletion with 6-hydroxydopamine were similar to those of reserpine. Experimentally induced hyper- and hypo-adrenergic states can result in regulation of the vascular .alpha.-adrenergic receptor through changes in receptor number or affinity.