Effect of nedocromil sodium on down-regulation of pulmonary beta-adrenoceptors.
1. We have studied the effect of the anti-inflammatory anti-asthma drug, nedocromil sodium, on down-regulation of pulmonary beta-adrenoceptors in guinea-pig lung. 2. Incubation of minced lung with isoprenaline (10 mumol/l) resulted in a reduction in maximum binding capacity of [125I]iodocyanopindolol to lung membranes from 246 +/- 4 to 169 +/- 6 fmol/mg of protein (mean +/- SEM, P less than 0.01, n = 18). 3. Nedocromil sodium, which had no direct effect on [125I]iodocyanopindolol binding, prevented isoprenaline-induced down-regulation, giving complete protection at a dose of 100 mumol/l. 4. The mechanism of this effect is not certain, but nedocromil sodium may interfere with the internalization of beta-adrenoceptors in pulmonary parenchymal cells. This may have some therapeutic relevance.
Kioumis
I
I
Department of Thoracic Medicine, National Heart and Lung Institute, London.
Ukena
D
D
Barnes
P J
PJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D006168:Guinea Pigs; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D017835:Nedocromil; D010869:Pindolol / Q000031:analogs & derivatives* / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015363:Quinolones; D011943:Receptors, Adrenergic, beta; D017835:Nedocromil; D020120:Iodocyanopindolol; D010869:Pindolol; D007545:Isoproterenol