Autoradiographical distribution of imidazoline binding sites in monoamine oxidase A deficient mice.
This study has used receptor autoradiography to characterize imidazoline binding sites (I-BS) in monoamine oxidase (MAO) A knockout and wild-type mice. A comparison between MAO-A and MAO-B, binding of the endogenous beta-carboline [(3)H]harmane, and I-BS, has been made using sections from brain and kidney. The loss of binding to MAO-A in the knockout animals was confirmed using the selective radioligand [(3)H]Ro41-1049, with labelling reduced to background levels. The binding of [(3)H]Ro19-6327 to MAO-B was unaffected, indicating no change in this isoform in response to the loss of MAO-A. A reduction in binding to the I(2)-BS, as labelled by both [(3)H]idazoxan and [(3)H]2-BFI (2-(2-benzofuranyl)-2-imidazoline), was seen in the MAO-A knockout animals in both brain and kidney sections, whereas binding to the I(1)-BS in kidney sections remained unchanged. The loss of I(2) binding was found to be regionally dependent and was positively correlated with the relative expression of MAO-A in specific regions in the wild-type animals. Using the MAO-A knockout mice it was also possible to demonstrate a non-MAO-A population of binding sites labelled by the putative I-BS endogenous ligand, harmane.
Department of Pharmacology, School of Medical Sciences, Bristol, UK. emma.s.j.robinson@bristol.ac.uk
Neil J
NJ
Anderson
Isabelle
I
Seif
David J
DJ
Nutt
Alan L
AL
Hudson
Emma S J
ES
Robinson
D000818:Animals; D001345:Autoradiography; D001572:Benzofurans / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006247:Harmine / Q000031:analogs & derivatives / Q000378:metabolism; D019329:Idazoxan / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism; D054755:Imidazoline Receptors; D048288:Imidazolines / Q000378:metabolism / Q000494:pharmacology; D007457:Iodine Radioisotopes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010848:Picolinic Acids / Q000378:metabolism; D011869:Radioligand Assay; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism
D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D048288:Imidazolines; D007457:Iodine Radioisotopes; D010848:Picolinic Acids; D011955:Receptors, Drug; D013844:Thiazoles; C063456:Ro 41-1049; C059303:lazabemide; D006247:Harmine; C103723:2-(2-benzofuranyl)-2-imidazoline; C005010:harman; D008995:Monoamine Oxidase; D019329:Idazoxan