Dissociation between I2-imidazoline receptors and MAO-B activity in platelets of patients with Alzheimer's type dementia.
The I2-imidazoline receptor is expressed in brain and platelets and could represent a new binding domain on MAO-B enzyme. Brain I2-imidazoline receptors and MAO-B sites have been found to be increased in Alzheimer's disease. The study sought to evaluate I2-imidazoline receptors and MAO-B activity in platelets from patients with Alzheimer's type dementia (ATD) and matched controls. Preliminary saturation experiments of [3H]idazoxan binding to platelet purified mitochondrial membranes were performed to determine the maximal number of binding sites (Bmax) and the apparent dissociation constant (Kd). Afterwards, the I2-imidazoline receptor density ([3H]idazoxan at 8 and 20 nM in the presence of 2 x 10(-6) M efaroxan) was evaluated in 20 patients with ATD and 17 controls. MAO-B activity was quantified by [14C]PEA oxidation. All subjects were screened for cognitive evaluation by the Mini-Mental State Examination. The density of I2-imidazoline receptors was similar in ATD patients (8.4 and 14.3 fmol/mg protein) and controls (8.3 and 14.0 fmol/mg protein). MAO-B activity was 22% higher in ATD subjects. Significant correlations between I2-imidazoline receptors and MAO-B activity were observed. No relationships between I2-imidazoline receptors or MAO-B activity and the cognitive score were observed. In conclusion, platelet I2-imidazoline receptors do not show the increase of I2-imidazoline receptors previously observed in brain of subjects with ATD. The dissociation between I2-imidazoline receptors and MAO-B in platelets suggests that the enzyme contributes to but not exclusively represents the I2-imidazoline receptor.
Soto
J
J
Department of Pharmacology, University of the Basque Country, Leioa, Bizkaia, Spain.
Ulibarri
I
I
Jauregui
J V
JV
Ballesteros
J
J
Meana
J J
JJ
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D001572:Benzofurans / Q000378:metabolism; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006801:Humans; D019329:Idazoxan / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism; D054755:Imidazoline Receptors; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000032:analysis / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D008995:Monoamine Oxidase; C062597:efaroxan; D019329:Idazoxan