RGD Reference Report - beta1, beta2, and beta3 adrenoceptors and Na+/H+ exchanger regulatory factor 1 expression in human bronchi and their modifications in cystic fibrosis. - Rat Genome Database
To date, three beta-adrenoceptor (beta-AR) subtypes have been identified, but only beta(1)-ARs and beta(2)-ARs have been characterized in human lungs. Moreover, beta(2)-ARs physically interact with the cystic fibrosis transmembrane conductance regulator (CFTR) through the Na(+)/H(+) Exchanger Regulatory Factor 1 (NHERF1) protein. beta(3)-ARs, which stimulate CFTR activity in transfected cells, have not been identified in human lungs. This study aimed (1) to characterize the presence of beta-AR subtypes, especially beta(3)-AR, in human bronchi, and (2) to compare their expression as well as that of NHERF1 in non-cystic fibrosis (CF) versus advanced CF lung samples. In human non-CF bronchi, beta(1)-AR, beta(2)-AR, beta(3)-AR, and NHERF1 transcripts and proteins were expressed mainly in bronchial epithelial cells. Those results were strengthened by the native expression of beta(1)-AR, beta(2)-AR, and beta(3)-AR in a human epithelial cell line, 16HBE14o(-). All beta-AR subtypes stimulated CFTR activity. In CF bronchi, we demonstrated beta(1)-AR and beta(3)-AR overexpression, and NHERF1 and beta(2)-AR underexpression. The origin of this protein remodeling (involving the physical or functional absence of CFTR, infection, inflammation, or high adrenergic tone) deserves further investigation. These results evidence for the first time, to the best of our knowledge, the presence of beta(3)-ARs in human bronchi, and suggest their usefulness as a putative new pharmacologic target in lung diseases where fluid homeostasis is altered. Furthermore, NHERF1 may be a new therapeutic target in patients with CF, to facilitate the trafficking of mutated CFTR to plasma membrane.