An endogenous clonidine-displacing substance from bovine brain: receptor binding and hypotensive actions in the ventrolateral medulla

Life Sci. 1986 Mar 24;38(12):1119-26. doi: 10.1016/0024-3205(86)90248-1.


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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood Pressure / drug effects*
  • Brain Chemistry*
  • Cattle
  • Cell Membrane / metabolism
  • Clonidine / analogs & derivatives
  • Clonidine / metabolism*
  • Clonidine / pharmacology
  • Epinephrine / metabolism
  • Heart Rate / drug effects
  • Imidazoline Receptors
  • Medulla Oblongata / drug effects
  • Medulla Oblongata / physiology*
  • Norepinephrine / metabolism
  • Receptors, Adrenergic / metabolism
  • Receptors, Adrenergic, alpha / metabolism
  • Receptors, Adrenergic, alpha-2*


  • Imidazoline Receptors
  • Receptors, Adrenergic
  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, alpha-2
  • apraclonidine
  • Clonidine
  • Norepinephrine
  • Epinephrine