Quantitative analysis of rat brain α2-receptors discriminated by [3H]clonidine and [3H]rauwolscine

Selective Increase of α2A‐Adrenoceptor Agonist Binding Sites in Brains of Depressed Suicide Victims

“…In contrast, in studies conducted with antagonist radioligands, the alteration has not been observed a 2-ADRENOCEPTORS IN DEPRESSION 1115 (Crow et al, 1984;Ferrier et a!., 1986;Ordway et al, 1994). Thus, the findings are suggestive of an increased proportion of the high-affinity conformation of the receptors (Asakura et a!., 1985). However, the direct involvement of the high-affinity state of the a2-adrenoceptor in depression and/or suicide has not been clarified as yet.…”

“…In contrast, the use of antagonist radioligands such as [3HI rauwolscine, [3Hj idazoxan, and [3Hjyohimbine (Crow eta!., 1984;Ferrier eta!., 1986;Ordway et a!., 1994) did not confirm the increased density of a 2-adrenoceptors observed with agonist radio!igands. In this context, some results have suggested that agonist radioligands label preferentially the highaffinity state of a2-adrenoceptors, whereas antagonist radioligands label both the high-and low-affinity states of this group of receptors (Asakura et al, 1985). Therefore, the increase in a2-adrenoceptor density observed in brains of depressed suicides with agonist radioligands could be related to an enhanced expression of the high-affinity conformation of the receptor.…”

Brain α2‐adrenoceptors in monoamine‐depleted rats: increased receptor density, G coupling proteins, receptor turnover and receptor mRNA

“…Previous studies have shown that chronic treatments with low doses of reserpine increase the affinity of agonist radioligands ([ 3 H]‐clonidine, [ 3 H]‐p‐aminoclonidine, [ 3 H]‐UK14304) for the brain α 2 ‐adrenoceptor, with no change in receptor density ( Hong et al ., 1988 ; Giralt & García‐Sevilla, 1989 ; Ugedo et al ., 1993 ), whereas acute treatments with high doses of reserpine have been associated with decreases in brain α 2 ‐adrenoceptor density, with no change in receptor affinity ( Kuno et al ., 1990 ). It is currently accepted that agonist radioligands label preferentially the high‐affinity state of α 2 ‐adrenoceptors, whereas antagonist radioligands label both the high‐ and low‐affinity states of this group of receptors ( Asakura et al ., 1985 ). Therefore, the increase in α 2 ‐adrenoceptor density observed in reserpine‐treated rats with the agonist radioligands [ 3 H]‐clonidine and [ 3 H]‐UK14304 as compared with the antagonist [ 3 H]‐RX821002 could be related to an enhanced expression of the high‐affinity conformation of the receptor.…”

Increased? 2;-adrenoceptor density in the frontal cortex of depressed suicide victims

“…Both types of analyses indicated that, in the range of concentrations used, only a single population of non-interacting binding sites (Hill number, nH=l.09+0.05, n=15) was present on the post-mortem cortical membranes. Under these experimental conditions the agonist [3H]clonidine appears to label preferentially the high affinity state of the az-adrenoceptor (a2H) (Asakura et al, 1985). …”