Specific decrease of high-affinity agonist states of alpha2-adrenoceptors in the aging mouse brain

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Abstract
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.