Clonidine-specific antisera recognize an endogenous clonidine-displacing substance in brain

Journal Article · Sat Apr 01 00:00:00 EST 1989 · Hypertension (Dallas); (United States)

DOI:https://doi.org/10.1161/01.HYP.13.4.341· OSTI ID:6156221

Meeley, M P; Towle, A C; Ernsberger, P; Char, L K; McCauley, P M; Reis, D J

An endogenous substance in brain, clonidine-displacing substance, binds to the same receptor populations as clonidine and is biologically active. Since receptor binding sites can be modeled by using specific antiligand antibodies, we tested the hypothesis that polyclonal antibodies raised in rat and rabbit against the clonidine analog p-aminoclonidine coupled to hemocyanin would recognize compounds structurally related to clonidine, including clonidine-displacing substance. Binding to anti-p-aminoclonidine antibodies was examined by using a competitive radioimmunoassay with tritiated p-aminoclonidine as the radioligand. Central vasodepressor agents that, like clonidine, are known to bind with high affinity to both imidazole sites and alpha 2-adrenergic receptors in brain inhibited radioligand binding to anti-p-aminoclonidine antibodies. All of these agents contain imidazol(in)e and phenyl ring moieties as part of their chemical structures (e.g., oxymetazoline); a number of other compounds without one or both of these rings failed to cross-react with the antisera. Clonidine-displacing substance, partially purified from bovine brain, also inhibited specific radioligand binding to anti-p-aminoclonidine antibodies. The inhibition was dose dependent and high affinity (IC50, 4 Units). The endogenous substance had no effect on the apparent affinity of the antibodies for the radioligand, but blocked a specific number of binding sites. Immunoprecipitation experiments showed that authentic clonidine-displacing substance, that which displaces tritiated p-aminoclonidine binding to membrane receptors, is recognized by anti-p-aminoclonidine antibodies.

• Research Organization: Cornell Univ. Medical College, New York, NY (USA)
• OSTI ID: 6156221
• Journal Information: Hypertension (Dallas); (United States), Vol. 13:4
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTIBODIES
RECEPTORS
ANTIHYPERTENSIVE AGENTS
BIOCHEMICAL REACTION KINETICS
BRAIN
DOSE-RESPONSE RELATIONSHIPS
IMMUNOGLOBULINS
LIGANDS
RADIOIMMUNOASSAY
RATS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRITIUM COMPOUNDS
ANIMALS
BODY
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DRUGS
GLOBULINS
IMMUNOASSAY
IMMUNOLOGY
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOASSAY
RADIOIMMUNOLOGY
REACTION KINETICS
RODENTS
TRACER TECHNIQUES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques