Visualization of high- and low-affinity beta-adrenergic receptors in rat lung: upregulation by chronic hypoxia.
Chronic hypoxia induces a hyperadrenergic state which down-regulates beta-adrenergic receptors (beta-AR) in the heart. We visualized lung beta-AR binding sites after adaptation to chronic hypoxia by autoradiography of whole lung sections labeled with 50 pM 125I-labeled pindolol. A low concentration of agonist (32 nM isoproterenol) selectively masked beta-ARs with high affinity for agonists. Total specific beta-AR binding increased twofold with hypoxia. In both the control and hypoxic lung sections, 60-70% of the beta-ARs were in a high-affinity state, which could be reversed by guanine nucleotide. Autoradiography revealed a high density of high- and low-affinity beta-AR sites in lung parenchyma, predominantly involving alveolar walls, but also the walls of airways and blood vessels. The distribution of high- and low-affinity beta-AR within the lung was qualitatively identical. Hypoxia increased beta-AR binding without affecting its distribution. The majority of the additional beta-ARs induced during adaptation to chronic hypoxia are in the high-affinity state, and are thus of probable functional significance.
Birnkrant
D J
DJ
Department of Pediatrics, Rainbow Babies and Children's Hospital, Cleveland, Ohio.
Davis
P B
PB
Ernsberger
P
P
D000818:Animals; D001345:Autoradiography; D002908:Chronic Disease; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D008297:Male; D010869:Pindolol / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012016:Reference Values; D012964:Sodium / Q000494:pharmacology; D015854:Up-Regulation
D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; D012964:Sodium; D010869:Pindolol; D007545:Isoproterenol