An endogenous clonidine-displacing substance from bovine brain: receptor binding and hypotensive actions in the ventrolateral medulla.
A substance has been isolated from bovine brain which displaces 3H-clonidine binding to rat brain membranes (clonidine-displacing substance; CDS). To determine whether CDS is similar to the antihypertensive agent clonidine, the in vitro binding properties of partially-purified CDS and its physiological action in the rostral ventrolateral medulla were examined. Like clonidine, CDS potently inhibited 3H-para-aminoclonidine binding to receptors in bovine ventrolateral medulla membranes (clonidine, IC50 = 24 +/- 8nM; CDS, IC50 = 0.30 +/- .10 Units), with highest affinity for non-adrenergic sites (clonidine, IC50 = 6 +/- 1nM; CDS, IC50 = 0.12 +/- .07 Units). CDS had no effect at beta-adrenergic or muscarinic cholinergic receptors. Like clonidine, CDS elicited a potent, reversible (less than 10 min) dose-dependent fall in arterial pressure (AP) and heart rate when microinjected specifically into the C1 area of the rostral ventrolateral medulla in the rat (maximum delta AP, -65 +/- 7 mm Hg). CDS represents an as-yet-uncharacterized endogenous, physiologically-active agent in brain which may participate in cardiovascular control via non-adrenergic receptors in the rostral ventrolateral medulla.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001923:Brain Chemistry; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D054755:Imidazoline Receptors; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2
D054755:Imidazoline Receptors; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D018341:Receptors, Adrenergic, alpha-2; C016986:apraclonidine; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine