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beta-Receptor numbers and thermodynamics in denervation supersensitivity
The Journal of Physiology
|January 1, 1981
Summary
Multiple system atrophy (MSA) causes denervation supersensitivity to adrenergic agonists due to increased beta-receptors. This study found more beta-receptors on lymphocytes in MSA patients, potentially explaining heart sensitivity to isoprenaline.
Area of Science:
- Neuroscience
- Pharmacology
- Cardiology
Background:
- Multiple system atrophy (MSA), also known as Shy-Drager Syndrome, is characterized by sympathetic nervous system degeneration.
- Denervation supersensitivity to adrenergic agonists is a known consequence of this degeneration.
Purpose of the Study:
- To investigate the supersensitivity to isoprenaline in patients with MSA.
- To quantify beta-adrenergic receptor numbers and affinity in MSA patients.
Main Methods:
- Assessed chronotropic response to isoprenaline in eight MSA subjects.
- Measured beta-receptor density and affinity using [H(3)]dihydroalprenolol ([H(3)]DHA) binding assays on lymphocytes from MSA and normal subjects.
- Analyzed the effect of temperature on [H(3)]DHA binding.
Main Results:
- MSA subjects exhibited supersensitivity to the heart's chronotropic effect of isoprenaline.
- Lymphocytes from MSA subjects showed an increased number of beta-receptors compared to normal subjects.
- Beta-receptor affinity for [H(3)]DHA was similar in both groups, and binding was entropy-driven.
Conclusions:
- Increased beta-receptor numbers on lymphocytes may reflect increased cardiac beta-receptors in MSA.
- This increase in cardiac beta-receptors could explain the observed denervation supersensitivity to isoprenaline in MSA patients with sympathetic degeneration.