β‐receptor numbers and thermodynamics in denervation supersensitivity

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Abstract
1. Denervation supersensitivity to adrenergic agonists occurs after degeneration of the sympathetic nervous system in the disease called multiple system atrophy (MSA) or the Shy Drager Syndrome.2. Supersensitivity to the chronotropic effect of i.v. isoprenaline on the heart was demonstrated in eight subjects with sympathetic nervous system degeneration and MSA.3. There was an increased number of β‐receptors present in MSA as measured by [H3]dihydroalprenolol ([H3]DHA) binding to β‐receptors on lymphocytes isolated from venous blood taken from the MSA subjects compared with [H3]DHA binding to lymphocytes from seven normal subjects. There was no difference in the affinity of lymphocyte β‐receptors for [H3]DHA in MSA.4. [H3]DHA binding to lymphocytes from MSA subjects was decreased at lower temperatures but was unaffected by lower temperatures in lymphocytes from normal subjects.5. Equilibrium constants for [H3]DHA binding to normal and MSA lymphocytes were similar, indicating that the affinity of the β‐receptors was similar in both groups. The equilibrium constants were little affected by cooling from 37 to 4 °C suggesting that the heat of reaction (enthalpy) for [H3]DHA binding was low. The Gibbs free energy change on binding was negative and similar in quantity for both normal and MSA lymphocytes. There was a similar, large, increase in entropy on binding of [H3]DHA to both normal and MSA lymphocytes, showing that the binding reaction was entropy driven.6. If lymphocyte β‐receptors reflect the status of cardiac β‐receptors, increased numbers of cardiac β‐receptors may contribute to the denervation supersensitivity to isoprenaline in MSA with sympathetic degeneration.