Indomethacin increases leucocyte beta-adrenoreceptors in man.
1. The effect of indomethacin, an inhibitor of prostaglandin synthesis, on number and sensitivity of alpha- and beta-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 or alpha-adrenoreceptors was measured by the specific binding of [3H]dihydroergocryptine to platelet membranes and that of beta-adrenoreceptors by the binding of [3H]dihydroalprenolol to leucocyte membranes. 4. The number of alpha-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 beta-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 beta-adrenoreceptor sites.
D000328:Adult; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D007213:Indomethacin