Beta‐adrenoceptors in human lung, bronchus and lymphocytes.
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1 The ability of propranolol, metoprolol, acebutolol, atenolol and practolol to reverse the stimulant effect of 10-5 M isoprenaline on lymphocyte cyclic AMP levels was determined. The ratios of doses required to produce 50% inhibition as compared with propranolol were 1:316 for metoprolol 1:1780 for acebutolol and 1:2820 for atenolol. No ratio could be calculated for practolol as it never produced more than 35% inhibition possibly because of its intrinsic sympathomimetic activity. This rank order of antagonist potencies suggest the lymphocyte β-receptor has β2 selectivity. 2 For peripheral airway smooth muscle isoprenaline, adrenaline and noradrenaline had relative EC50s of 1:25:9290 respectively in the absence of uptake blockade. However, the EC50s changed to 1:15:82 in the presence of neuronal uptake blockade and x-adrenoceptor blockade. These observations are consistent with β2 selectivity. Salbutamol behaved as a partial agonist on peripheral airway smooth muscle. It was possible to demonstrate competitive antagonism to isoprenaline. Estimates of the dissociation constant of salbutamol were obtained (6.6 ± 0.02) × 10-7 M, n=4, mean ± s.e. mean). 3 A novel technique for determining the pA2 is described which is particularly useful on peripheral airway smooth muscle. Values obtained for propranolol and practolol using this technique were: propranolol pA2 7.83 ± 0.14; slope=0.97 ± 0.05 (n=4), practolol pA2 5.62 ± 0.15; slope=1.17 ± 0.17 (n=4) These values support the β2 selectivity suggested by the agonist studies. 4 The cyclic AMP response of lung parenchyma to β-adrenoceptor agonists and antagonists (in the presence of isoprenaline demonstrated β2 selectivity. Salbutamolol appeared to be a partial agonist when compared with the cyclic AMP response to isoprenaline. 5 The β-adrenoceptors of the lymphocyte, bronchial smooth muscle and lung parenchyma have β2 selectivity although they differ somewhat quantitatively from each other.
