Para-azidoclonidine: a novel photoaffinity ligand for the alpha 2-receptor

Reversible and irreversible interactions of the photoreactive clonidine analogue p-azidoclonidine (PAZC) with brain alpha 2-adrenergic receptors were examined. In the absence of light, PAZC displayed selective, high affinity, competitive interactions with sites labeled by the alpha 2-agonist 3H-p-aminoclonidine (3H-PAC). Reversible binding characteristics resembled those of other alpha 2-agonists. Preincubation of bovine frontal cortex membranes with 100 nM PAZC followed by ultraviolet irradiation and thorough washing decreased alpha 2-receptor density 42% relative to controls receiving irradiation alone. The loss of receptors could be prevented by inclusion of 500 nM phentolamine in the preincubation medium. Alpha 1- and beta-adrenergic receptors were relatively unaffected. PAZC is a potential photoaffinity ligand for the alpha 2-adrenergic receptor.