Dolichol alters GABA uptake and high affinity binding of agonist to rat brain synaptic plasma membranes.
The effects of dolichol on high affinity [3H]muscimol binding to synaptic plasma membrane (SPM) and [3H]GABA uptake into synaptosomes from rat brain were analyzed. Membranes were enriched with dolichol, by preincubation, in the presence of bovine serum albumin (BSA) as a vehicle (40-100 micrograms of dolichol/mg protein + 5% BSA). The rate of dolichol incorporation into the membrane was determined using [1-3H]dolichol C95, and it was in the range of 5-7 nmol/mg protein/h for synaptosomes and SPM, respectively. The uptake of [3H]GABA into synaptosomes enriched with dolichol decreased significantly by about 30%. Dolichol alone added into the incubation medium produced only a negligible effect. Specific binding of [3H]muscimol, which was higher than 90% of total binding, was significantly reduced to SPM enriched with dolichol as compared to controls. The Kd of the high affinity sites was significantly elevated by about 30% in SPM enriched with dolichol (10.8 +/- 0.3 nM vs 7.3 +/- 0.2 nM in control). This difference was more pronounced for SPM isolated from cerebellum (Kd increased by about 50%). The Bmax value was not changed. Dolichol alone did not alter the agonist binding. These results indicate for the first time that the higher level of dolichol in SPM might influence the GABAergic transmission system. An increase in dolichols in membranes may be an important factor in the decline of brain function during aging.
Strosznajder
J
J
Department of Neurochemistry, Polish Academy of Sciences, Warsaw.
Samochocki
M
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004286:Dolichols / Q000494:pharmacology*; D008297:Male; D009118:Muscimol / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics*
D004286:Dolichols; D011976:Receptors, Muscarinic; D009118:Muscimol; D005680:gamma-Aminobutyric Acid