Subcellular distribution of beta-adrenoceptors in brain following administration of antidepressant drugs.
The distribution of specific binding of [3H]dihydroalprenolol([3H]DHA) in sucrose gradients (0.2-1.75 M), containing homogenates of the cortex of rat brain, centrifuged to equilibrium (110,000 g/16 hr), was examined in controls and after treatment with antidepressant drugs. There were no significant changes in the specific binding of [3H]DHA after acute administration of desipramine (DMI, 50 mg/kg) or clorgyline (20 mg/kg), either in terms of the number of receptors or distribution in the sucrose gradient. There was a significant decrease (29%) in the number of beta-adrenoceptors after the chronic regimen with DMI, but again no apparent alteration in the density of the receptor-containing membranes, both samples having a maximum distribution at approximately 1.1 M sucrose. Non-specific binding was maximal at 0.65 M sucrose. Electron microscopy showed that the non-specific binding was largely to myelin and the fraction containing most specific binding was composed of membrane fragments. The activity of Na+ K+ ATPase had a single broad peak (maximum at 1.1 M sucrose). Thus, at the times studied, in vivo desensitisation/internalisation of cortical beta-adrenoceptors did not apparently occur following large acute doses of antidepressant drugs and furthermore the down-regulation which followed the chronic regimen with DMI did not involve migration of receptors into "light density fractions" which are reported to be present after acute exposure to agonists in vitro.
Koshikawa
N
N
Institute of Psychiatry, London, U.K.
Durcan
M J
MJ
Weaver
K
K
Lawrence
K
K
Campbell
I C
IC
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D004082:Dihydroalprenolol / Q000378:metabolism; D008297:Male; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism*
D000928:Antidepressive Agents; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D003891:Desipramine