1. The effect of indomethacin, an inhibitor of prostaglandin synthesis, on number and sensitivity of α- and β-adrenoreceptors was studied in normal healthy volunteer subjects.
2. The subjects were studied under metabolic conditions. To achieve inhibition of prostaglandin synthesis indomethacin (2 mg day−1 kg−1) was given orally for 7 days. This dose decreased urinary excretion of prostaglandin E-like immunoreactivity by 70%.
3. The number of α-adrenoreceptors was measured by the specific binding of [3H]dihydroergocryptine to platelet membranes and that of β-adrenoreceptors by the binding of [3H]dihydroalprenolol to leucocyte membranes.
4. The number of α-adrenoreceptors did not change with indomethacin, nor did basal, prostaglandin E1- or noradrenaline-stimulated cyclic AMP production by platelet membranes. In contrast, the number of β-adrenoreceptors increased by 92%. Indomethacin did not affect, however, basal, 1-isoprenaline- or prostaglandin E1-stimulated cyclic AMP production in leucocyte membranes.
5. These results suggest that a reflex-mediated decrease in sympathetic discharge in response to an indomethacin-induced decrease in release of vasodilator prostaglandins may lead to an ‘up-regulation’ of β-adrenoreceptor sites.