Age-dependent changes in beta-adrenergic receptor subtypes and adenylyl cyclase activation in adipocytes from Fischer 344 rats
| Autor: | Kiefer W. Daniel, Veronica Prpic, Thomas W. Gettys, Sheila Collins, Elizabeth M. Rohlfs, Ian L. Taylor |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Glycerol
Male Aging medicine.medical_specialty Epinephrine Adrenergic receptor Lipolysis Blotting Western Molecular Sequence Data Adrenergic Alpha (ethology) Dioxoles Biology Polymerase Chain Reaction Beta-1 adrenergic receptor Adenylyl cyclase chemistry.chemical_compound Endocrinology GTP-Binding Proteins Internal medicine Receptors Adrenergic beta Adipocytes medicine Animals RNA Messenger Beta (finance) DNA Primers Epididymis Forskolin Base Sequence Cell Membrane Adrenergic beta-Agonists Rats Inbred F344 Rats Enzyme Activation Kinetics Adipose Tissue chemistry 3' 5'-Cyclic-AMP Phosphodiesterases Ethanolamines Phenylisopropyladenosine Adenylyl Cyclases |
| Zdroj: | Endocrinology. 136:2022-2032 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/endo.136.5.7720650 |
| Popis: | Epididymal adipocytes were isolated from Fischer 344 rats aged 3, 6, 12, and 24 months, to study the mechanisms responsible for age-dependent diminution in cellular adrenergic responsiveness. Messenger RNA (mRNA) levels for the beta 1-, beta 2-, and beta 3-adrenergic receptors (ARs) were compared across age groups and related to adenylyl cyclase activation by selective receptor agonists in adipocyte plasma membranes and activation of lipolysis in intact cells. mRNA levels for the beta 1-AR decreased by 60% between 3-6 months and remained at this reduced level through 12 and 24 months. A modest increase in beta 2-AR mRNA was noted between 3-12 months, but decreased between 12-24 months to levels seen in the 3-month-old group. mRNA for the beta 3-AR did not change between 3-6 months, but decreased by about 40% between 6-12 months, and by a further 50% between 12-24 months. Lipolytic responsiveness also diminished with age, and regardless of whether beta 3-selective or beta 1/beta 2-selective agonists were used, the maximal release of glycerol was most severely blunted in adipocytes from 24-month-old rats. The age-dependent changes in adenylyl cyclase activation by beta-adrenergic agonists mirrored the observed changes in lipolytic responsiveness with respect to diminished efficacy. These results together with the similar forskolin-stimulated adenylyl cyclase activity among the groups suggest age-dependent changes in activation of adenylyl cyclase at a prior step. This suggestion is also supported by the comparable inhibitory capacities of the alpha 2-adrenergic and A1-adenosine signaling systems among the age groups. In view of the similar levels of Gs alpha, the age-dependent decrease in adrenergic responsiveness in rat adipocytes appears to result primarily from specific decreases in the expression of both beta 3-AR and beta 1-ARs. |
| Databáze: | OpenAIRE |
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