Isolation and partial purification of a clonidine-displacing endogenous brain substance.
A new compound, designated clonidine-displacing substance (CDS), has been isolated from calf brain by ion-exchange chromatography, zone electrophoresis and high-performance liquid chromatography. CDS binds specifically to alpha 2-adrenergic receptors in rat brain and human platelet membranes, as measured in direct binding experiments using [3H]clonidine and [3H]yohimbine respectively. Unlike clonidine or other alpha 2-agonists, CDS does not affect basal levels of adenylate cyclase in human platelets at the highest concentrations obtainable. The apparent molecular mass of the compound is estimated to be 500 +/- 50 Da, as determined by gel-filtration chromatography on Sephadex G-15. The new compound is thermostable, not affected by proteolytic enzymes, such as trypsin, chymotrypsin, pronase, papain and pyroglutamase, or by boiling in 0.2 M HCl for 5 min. It does not bind to alpha 1-receptors in rat brain or to beta-adrenergic receptors in turkey erythrocytes, since it is unable to displace [3H]prazosin and [125I]cyanopindolol from alpha 1 and beta-receptors respectively.
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001667:Binding, Competitive; D001792:Blood Platelets / Q000201:enzymology; D001923:Brain Chemistry; D002417:Cattle; D002845:Chromatography / Q000379:methods; D003000:Clonidine / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D054755:Imidazoline Receptors; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D008970:Molecular Weight; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2; D014422:Turkeys; D015016:Yohimbine / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D054755:Imidazoline Receptors; D011942:Receptors, Adrenergic, alpha; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D020120:Iodocyanopindolol; D010869:Pindolol; D003000:Clonidine; D011224:Prazosin