Isolation of an endogenous clonidine‐displacing substance from rat brain

Abstract

An endogenous substance which specifically displaces clonidine, yohimbine and rauwolscine from rat brain cyz-adrenergic receptors, has been isolated. The new compound, designed clonidine-displacingsubstance (CDS), has been partially purified by ion exchange chromatography, zone electrophoresis and high performance liquid chromatography (HPLC). CDS binds specifically to cYz-adrenergic receptors by competing with either cuz-adrenergic agonists or cYz-antagonists, but has no effect on the specific binding of [3H]prazosin to cYr-adrenergic receptors in rat brain membranes. In the course of isolation, CDS was shown to be neither the endogenous neurotransmitter (-)norepinephrine (NE) nor the guanyl nucleotide GTP which lowers the specific binding of cYz-agonists to the cus-adrenergic receptors. Clonidine cYrAdrenergic receptor Yohimbine

The effect of the putative endogenous imidazoline receptor ligand, clonidine‐displacing substance, on insulin secretion from rat and human islets of Langerhans

“…Assessment of the amount of CDS present in each preparation was assayed with the membrane fraction of rat brain prepared as described above. One unit of CDS activity is defined as the amount required to displace 50% of specifically bound [ 3 H]‐clonidine (2 nM) in the presence of 10 μM noradrenaline, from rat brain membranes (100 μg) incubated in a volume of 100 μl of 50 mM Tris‐HCl buffer, pH 7.5, at 25°C for 40 min (Atlas & Burstein, 1984). Thus, varying dilutions of each CDS preparation were incubated with the radioligand and brain membranes.…”

Endogenous β‐Carbolines as Clonidine‐Displacing Substances

“…Atlas and Burnstein4,7 undertook the first experiments to ascertain whether there was an endogenous compound that had clonidine‐like activity. A methanolic extraction of rat7 and bovine4 brain, followed by reverse‐phase high performance liquid chromatography (RP‐HPLC) purification yielded a partially purified extract exhibiting such activity. This substance, termed classical CDS, was divided into the crude and the RP‐HPLC‐pure forms.…”

Central imidazoline (I1) receptors as targets of centrally acting antihypertensives

“…The possibility that I 1 -and ␣ 2 -adrenoceptors are located in series along the same cardiovascular pathway [30] has already been mentioned. [40][41][42]. CDS was therefore proposed as an endogenous receptor stimulant, possibly involved in cardiovascular control via non-adrenergic receptors in the RVLM.…”