SPECIFIC DECREASE OF HIGH-AFFINITY AGONIST STATES OF ALPHA2-ADRENOCEPTORS IN THE AGING MOUSE-BRAIN

Using the specific binding of the full alpha2-adrenergic agonist3H-UK-14,304 the contribution of high-affinity agonist states to the total number of alpha2-adrenoceptors as labeled by the specific binding of the antagonist3H-yohimbine has been investigated in the brain of young and aged mice. In contrast to findings with human platelet membranes, in young mice all central alpha2-adrenoceptors are present in a high-affinity agonist conformation. While the total number of alpha2-adrenoceptors was not changed in the brain of aged animals, a specific decline of the high-affinity agonist sites by about 30% was observed. It is suggested that the specific decrease of high-affinity agonist sites of central alpha2-adrenoceptors might represent one of the mechanisms leading to a general impairment of central noradrenergic neurotransmission with aging. © 1990 Springer-Verlag.