An endogenous substance with clonidine-like properties: selective binding to imidazole sites in the ventrolateral medulla.
We sought to characterize the interactions of an endogenous clonidine-displacing substance (CDS) with the specific receptor sites to which clonidine and its analogs bind: (a) the non-adrenergic imidazole binding site, which is present in the ventrolateral medulla (VLM) but not the frontal cortex, (b) high-affinity and (c) low-affinity states of the alpha 2-adrenergic receptor, and (d) the alpha 1-adrenergic receptor. CDS, like clonidine, potently and completely inhibited specific p-[3H]aminoclonidine binding to membranes from the VLM or from the frontal cortex. Both CDS and clonidine bound with highest affinity to imidazole binding sites in the VLM, both were 3-fold selective for high-affinity over low-affinity alpha 2-adrenergic receptors, and both exhibited lowest affinity for alpha 1-adrenergic receptors. Unlike clonidine, CDS exhibited 30-fold selectivity for imidazole over alpha 2-adrenergic receptors but showed only a weak preference for alpha 2- over alpha 1-adrenergic receptors, indicating that CDS and clonidine are not identical. We conclude that CDS is an endogenous clonidine-like substance which may be the natural ligand for imidazole binding sites in the VLM. The receptor-binding properties of CDS are consistent with the view that it is a unique and as yet unrecognized compound.
Ernsberger
P
P
Laboratory of Neurobiology, Cornell University Medical College, New York, NY 10021.
Meeley
M P
MP
Reis
D J
DJ
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D003000:Clonidine / Q000378:metabolism*; D007093:Imidazoles / Q000302:isolation & purification / Q000378:metabolism*; D054755:Imidazoline Receptors; D007700:Kinetics; D008526:Medulla Oblongata / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2
D007093:Imidazoles; D054755:Imidazoline Receptors; D011942:Receptors, Adrenergic, alpha; D018341:Receptors, Adrenergic, alpha-2; D003000:Clonidine