Hypotensive action of clonidine analogues correlates with binding affinity at imidazole and not alpha-2-adrenergic receptors in the rostral ventrolateral medulla.
Clonidine acts within the rostral ventrolateral medulla to lower arterial pressure. The receptor mechanism for this action is unknown. In the rostral ventrolateral medulla clonidine binds not only to the alpha 2-adrenergic receptor but also to a novel class of sites which are specific for imidazolines and imidazoles and are distinct from adrenergic or histaminergic receptors. In order to distinguish whether a putative imidazole receptor or the alpha 2-receptor mediates the clonidine hypotensive response, a series of clonidine analogues were tested (1) in radioligand binding assays of their affinity at imidazole and alpha 2-adrenergic receptors, and (2) by microinjection into the rostral ventrolateral medulla of anaesthetized rats to measure their capacity to lower arterial pressure. The hypotensive response elicited by the test agents was strongly correlated with affinity at imidazole sites (r = 0.92) but not with alpha 2-adrenergic affinity (r = 0.36). An imidazole receptor in the rostral ventrolateral medulla may participate in the hypotensive action of clonidine.
Ernsberger
P
P
Division of Neurology, Cornell University Medical College, New York, NY 10021.
Giuliano
R
R
Willette
R N
RN
Granata
A R
AR
Reis
D J
DJ
D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D007093:Imidazoles / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D008845:Microinjections; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; D003000:Clonidine