Clonidine-specific antibodies as models for imidazole and alpha 2-adrenergic receptor binding sites: implications for the structure of clonidine-displacing substance.
Polyclonal antisera raised against para-aminoclonidine coupled to haemocyanin exhibit high affinity for para-aminoclonidine, clonidine and chloroethylclonidine (IC50 less than 100 nmol/l). Anti-para-aminoclonidine antibodies also cross-react with naphazoline, oxymetazoline and tolazoline at moderate concentrations (IC50, 300-500 mumol/l); the phenyl-imidazoles detomidine, medetomidine and MPV830 are weakly cross-reactive (IC50 greater than 0.2 mmol/l). All of these compounds bind with high affinity to both imidazole and alpha 2-adrenergic receptors. Compounds which are imidazole- or alpha 2-specific do not cross-react with anti-para-aminoclonidine antibodies (IC50 greater than 1 mmol/l). Anti-para-aminoclonidine also recognizes an endogenous clonidine-displacing substance in the brain. Thus, (a) binding to anti-para-aminoclonidine antibodies defines a subset of phenyl-imidazol(in)e ligands which bind to both imidazole and alpha 2-adrenergic receptors, suggesting that anti-para-aminoclonidine recognition sites resemble a hybrid of the two receptor types; (b) antibodies to imidazole- or alpha 2-specific agents may be useful as models for differentiating between these types; (c) since clonidine-displacing substance is recognized by anti-para-aminoclonidine antibodies, it may have phenyl and imidazole rings as parts of its chemical structure.
Meeley
M P
MP
Division of Neurobiology, Cornell University Medical College, New York, NY 10021.
Ernsberger
P
P
McCauley
P M
PM
Reis
D J
DJ
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D003000:Clonidine / Q000276:immunology* / Q000378:metabolism*; D000939:Epitopes; D007093:Imidazoles / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*
D000939:Epitopes; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; D003000:Clonidine