Imidazoline receptors in vascular smooth muscle and endothelial cells.

We sought to determine if smooth muscle and endothelial cells of blood vessels express imidazoline receptors. Membranes of cultured smooth muscle cells specifically bind with high affinity to alpha 2-adrenergic ligands, [3H]p-aminoclonidine, [3H]rauwolscine, and [3H]idazoxan. All of [3H]rauwolscine and [3H]p-aminoclonidine but less than 10% of [3H]idazoxan binding was displaced by 10 microM epinephrine, indicating a nonadrenergic binding site for [3H]idazoxan. [3H]Idazoxan binding was inhibited with a rank order of potency: cirazoline > idazoxan > naphazoline >> guanabenz > amiloride > clonidine = phentolamine. Agmatine, an endogenous ligand for I-receptors, inhibited binding with a Ki of 240 +/- 25 nM. The binding of [3H]idazoxan to membranes of pulmonary artery endothelial cells was to both alpha 2-adrenergic and imidazoline receptors. Cultured smooth muscle cells, as well as rat carotid arterioles, were specifically immunostained by antibodies to an I-receptor-associated protein. We conclude that vascular smooth muscle and endothelial cells express not only alpha 2-adrenergic receptors but also I-receptors of the I2 subclass with high affinity for agmatine. Since serum contains an endogenous ligand for I-receptors, possibly agmatine, the results suggest the presence of a novel receptor mechanism on vascular smooth muscle which may regulate vascular tone.