Comparison of the Properties of Agmatine and Endogenous Clonidine-Displacing Substance at Imidazoline and Alpha-2

Nonadrenergic imidazoline receptors (I receptors) mediate the central antihypertensive effects of clonidine. Agmatine, an ar-ginine metabolite that is synthesized within bovine brain and exhibits clonidine-displacing substance (CDS) activity, might be the endogenous I receptor neurotransmitter. The authors compared the affinity of agmatine versus the potency of endo-genous bovine hypothalamic CDS, at bovine adrenomedullary l receptors and at human clonidine-binding sites: human a!-pha-2A, alpha-2B and a!pha-2C expressed on transfected cell lines, I sites on human platelet plasma membranes and 12b (amiloride-insensitive) sites on human platelet intracellular membranes. The aipha-2 and I, sites were labeled with [1251]p-iodoclonidine and the ‘2b sites were labeled with rH]-idazoxan. Agmatine displayed preferential affinity for l receptors, with both high (H) and low (L) affinity components; the rank orde