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Specific decrease of high-affinity agonist states of alpha 2-adrenoceptors in the aging mouse brain.

C M Gelbmann1, W E Müller

  • 1Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Federal Republic of Germany.

Journal of Neural Transmission. General Section
|January 1, 1990
PubMed
Summary
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Aging reduces high-affinity agonist sites on central alpha 2-adrenoceptors in mice by 30%. This decline in alpha 2-adrenoceptors may impair noradrenergic neurotransmission with age.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Aging Research

Background:

  • Alpha 2-adrenoceptors play a crucial role in central noradrenergic neurotransmission.
  • These receptors can exist in different affinity states for agonists, influencing their function.
  • Understanding changes in receptor states with aging is vital for comprehending age-related neurological changes.

Purpose of the Study:

  • To investigate the contribution of high-affinity agonist states to the total alpha 2-adrenoceptors in the brains of young and aged mice.
  • To determine if aging affects the proportion of alpha 2-adrenoceptors in high-affinity agonist conformations.

Main Methods:

  • Utilized radioligand binding assays with a specific alpha 2-adrenergic agonist (3H-UK-14,304) and antagonist (3H-yohimbine).
  • Compared receptor binding characteristics in brain tissue from young and aged mice.

Related Experiment Videos

  • Quantified total alpha 2-adrenoceptors and high-affinity agonist-bound states.

    • Main Results:

    • In young mice, all central alpha 2-adrenoceptors were found in a high-affinity agonist conformation.
    • The total number of alpha 2-adrenoceptors remained unchanged in aged mice compared to young mice.
    • A significant decline of approximately 30% in high-affinity agonist sites was observed in the brains of aged mice.

    Conclusions:

    • Central alpha 2-adrenoceptors in young mice exist exclusively in a high-affinity agonist state.
    • Aging is associated with a specific reduction in these high-affinity agonist sites, not the total receptor number.
    • This decrease in high-affinity agonist sites may contribute to the age-related impairment of central noradrenergic neurotransmission.