Alpha 1-adrenoceptor function and autoradiographic distribution in human asthmatic lung.
1. The autoradiographic distribution of alpha 1-adrenoceptors was investigated in non-diseased and asthmatic human lung by use of [3H]-prazosin (H-PZ). To validate binding and autoradiographic methods, H-PZ binding was also measured in rat heart. 2. Significant levels of specific H-PZ binding were detected in sections of rat heart. This binding was associated with a single class of non-interacting sites of high affinity (dissociation constant, Kd = 1.17 +/- 0.26 nM). The maximum binding capacity (Bmax) was 59.5 +/- 4.5 fmol mg-1 protein. 3. In sharp contrast, very low levels of specific H-PZ binding were found in both human nondiseased and asthmatic bronchus, although a high level of binding of [125I]-iodocyanopindolol (I-CYP, 50 pM) to beta-adrenoceptors was detected in these airways. Furthermore, very low levels of autoradiographic grains representing specific H-PZ binding were found in all airway structures in human non-diseased or asthmatic lung parenchyma. 4. Consistent with these data, the alpha-adrenoceptor agonist phenylephrine failed to induce significant increases in tone in bronchi isolated from either non-diseased or asthmatic human lung. Results indicate that asthma does not involve significant increases in airway alpha 1-adrenoceptor function.
Spina
D
D
Department of Pharmacology, University of Western Australia, Perth.
Rigby
P J
PJ
Paterson
J W
JW
Goldie
R G
RG
D000328:Adult; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001345:Autoradiography; D001980:Bronchi / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives; D011224:Prazosin / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism / Q000502:physiology*; D013806:Theophylline / Q000494:pharmacology
D007457:Iodine Radioisotopes; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D020120:Iodocyanopindolol; D002217:Carbachol; D011433:Propranolol; D010869:Pindolol; D013806:Theophylline; D007545:Isoproterenol; D011224:Prazosin