[3H]p-aminoclonidine and [3H]idazoxan label different populations of imidazoline sites on rat kidney.
In the presence of RS-15385-197 to preclude binding to alpha 2-adrenoceptors, [3H]p-aminoclonidine labelled a low affinity high capacity site, (Kd = 127.6 +/- 19.7 nM, Bmax 978 +/- 172 fmol/mg protein) whereas [3H]idazoxan labelled a high affinity low capacity site (Kd = 1.66 +/- 0.28 nM, Bmax 45.3 +/- 11.4 fmol/mg protein). Clonidine and p-aminoclonidine showed moderate affinity for the site labelled by [3H]p-aminoclonidine, but low affinity for the site labelled by [3H]idazoxan, whereas idazoxan showed high affinity for [3H]idazoxan and low affinity for [3H]p-aminoclonidine binding. Naphazoline inhibited [3H]idazoxan in a biphasic manner suggesting that [3H]idazoxan may label an heterogeneous population of imidazoline sites. GTP inhibited [3H]idazoxan but not [3H]p-aminoclonidine binding. These results suggest that [3H]idazoxan labelled imidazoline I2 binding sites, whereas [3H]p-aminoclonidine labelled a novel subtype which showed marked differences to the imidazoline I1 binding site reported in bovine and human brainstem.
MacKinnon
A C
AC
Department of Pharmacology, Syntex Research Centre, Riccarton, Edinburgh, UK.
Stewart
M
M
Olverman
H J
HJ
Spedding
M
M
Brown
C M
CM
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D003000:Clonidine / Q000031:analogs & derivatives*; D004146:Dioxanes; D006160:Guanosine Triphosphate / Q000494:pharmacology; D019329:Idazoxan; D007093:Imidazoles / Q000378:metabolism*; D054755:Imidazoline Receptors; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009278:Naphazoline / Q000494:pharmacology; D009287:Naphthyridines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000378:metabolism*; D014316:Tritium
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007093:Imidazoles; D054755:Imidazoline Receptors; D007546:Isoquinolines; D009287:Naphthyridines; D011955:Receptors, Drug; D014316:Tritium; C016986:apraclonidine; D006160:Guanosine Triphosphate; D009278:Naphazoline; C060956:Delequamine; D003000:Clonidine; D019329:Idazoxan