Autoradiographic localization of beta-adrenoceptors in asthmatic human lung.
The autoradiographic distribution and density of beta-adrenoceptors in human non-diseased and asthmatic bronchi were investigated using [125I]iodocyanopindolol (I-CYP). Analysis of the effects of the beta-adrenoceptor antagonists on I-CYP binding demonstrated that betaxolol (20 nM, beta 1-selective) had no significant effect on specific grain density in either nonasthmatic or asthmatic human bronchus, whereas ICI-118551 (20 nM, beta 2-selective) inhibited I-CYP binding by 85 +/- 9% and 89 +/- 3%, respectively. Thus, homogeneous populations of beta 2-adrenoceptors existed in bronchi from both sources. Large populations of beta-adrenoceptors were localized to the bronchial epithelium, submucosal glands, and airway smooth muscle. Asthmatic bronchial tissue featured epithelial damage with exfoliated cells associated with luminal mucus plugs. A thickened basement membrane and airway smooth muscle hyperplasia were also evident. High levels of specific I-CYP binding were also detected over asthmatic bronchial smooth muscle, as assessed by autoradiography and quantitation of specific grain densities. Isoproterenol and fenoterol were 10- and 13-fold less potent, respectively, in bronchi from asthmatic lung than in those from nonasthmatic lung. However, this attenuated responsiveness to beta-adrenoceptor agonists was not caused by reduced beta-adrenoceptor density in asthmatic airways. A defect may exist in the coupling between beta-adrenoceptors and postreceptor mechanisms in severely asthmatic lung.
Spina
D
D
Department of Pharmacology, University of Western Australia, Nedlands, Perth.
Rigby
P J
PJ
Paterson
J W
JW
Goldie
R G
RG
D001249:Asthma / Q000378:metabolism*; D001345:Autoradiography; D006801:Humans; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D008168:Lung / Q000378:metabolism*; D010869:Pindolol / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012016:Reference Values
D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol