Selective increase of alpha2A-adrenoceptor agonist binding sites in brains of depressed suicide victims.
The alpha2A- and alpha2C-adrenoceptor subtypes were evaluated in postmortem brains from suicides with depression (n = 22), suicides with other diagnoses (n = 12), and controls (n = 26). Membrane assays with the antagonist [3H]RX821002 (2-[3H]methoxyidazoxan) suggested the presence of alpha2A-adrenoceptors in the frontal cortex and both alpha2C-adrenoceptors and alpha2A-adrenoceptors in the caudate. The proportions in caudate were similar in controls (alpha2A, 86%; alpha2C, 14%), depressed suicides (alpha2A, 91%; alpha2C, 9%), and suicides with other diagnoses (alpha2A, 88%; alpha2C, 12%). Autoradiography of [3H]RX821002 binding under alpha(2B/C)-adrenoceptor-masking conditions confirmed the similar densities of alpha2A-adrenoceptors in the cortex, hippocampus, and striatum from controls and suicides. In the frontal cortex of depressed suicides, competition of [3H]RX821002 binding by (-)-adrenaline revealed a greater proportion (61 +/- 9%) of alpha2A-adrenoceptors in the high-affinity conformation for agonists than in controls (39 +/- 5%). Simultaneous analysis with the agonists [3H]clonidine and [3H]UK14304 and the antagonist [3H]RX821002 in the same depressed suicides confirmed the enhanced alpha2A-adrenoceptor density when evaluated by agonist, but not by antagonist, radioligands. The results indicate that depression is associated with a selective increase in the high-affinity conformation of the brain alpha2A-adrenoceptors.
Callado
L F
LF
Department of Pharmacology, University of the Basque Country, Leioa, Bizkaia, Spain.
Meana
J J
JJ
Grijalba
B
B
Pazos
A
A
Sastre
M
M
García-Sevilla
J A
JA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000328:Adult; D001345:Autoradiography; D001667:Binding, Competitive; D001923:Brain Chemistry / Q000502:physiology*; D000068438:Brimonidine Tartrate; D002462:Cell Membrane / Q000737:chemistry; D003000:Clonidine / Q000494:pharmacology; D003863:Depression / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011810:Quinoxalines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013405:Suicide; D014316:Tritium
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D014316:Tritium; D000068438:Brimonidine Tartrate; C058525:2-methoxyidazoxan; D003000:Clonidine; D019329:Idazoxan