Published ahead of print on June 10, 2004, doi:10.1165/rcmb.2004-0035OC
© 2004 American Thoracic Society DOI: 10.1165/rcmb.2004-0035OC Expression and Functions of the Duodenal Peptide Secretin and its Receptor in Human Lung Pharmagene Laboratories, Royston, Hertfordshire; and Department of Infectious Disease, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom Address correspondence to: Richard Davis, Pharmagene Laboratories, 2 Orchard Road, Royston, Hertfordshire SG8 5HD, UK. E-mail: richard.davis{at}pharmagene.com The physiological role of the duodenal peptide secretin is as a potent stimulant of electrolyte and water movement in pancreatic and biliary epithelium, via activation of G protein–coupled secretin receptors (hSCTR). However, the distribution and potential function of hSCTR in human lung has not previously been addressed. Using real-time quantitative reverse transcriptase–polymerase chain reaction profiling, in situ hybridization, and immunohistochemistry, we demonstrated that the hSCTR is abundantly expressed within the distal regions of human lung (tertiary bronchus and parenchyma), with negligible expression detected in more proximal regions (trachea, primary, and secondary bronchus). Expression was observed predominantly on the basolateral membrane of the bronchial epithelial layer, with some expression also observed in bronchial smooth muscle. In primary cultures of human tertiary bronchial epithelial cells, secretin was demonstrated to potently stimulate channel-mediated Cl– efflux in a concentration-dependent manner. Secretin was also shown to cause concentration-dependent relaxation of human tertiary bronchial smooth muscle. In summary, these data demonstrate that secretin receptors are present in human lung, and that activation of these receptors with human secretin potently stimulates concentration-dependent Cl– efflux from bronchial epithelial cells and bronchorelaxation.
Abbreviations: airway surface liquid, ASL • cystic fibrosis, CF • CF transmembrane regulator, CFTR • chloride ion, Cl– • Dulbecco's minimum essential medium, DMEM • digoxygenin, DIG • human secretin receptor, hSCTR • industrial methylated spirits, IMS • pituitary adenylate cyclase–activating polypeptide, PACAP • real-time, quantitative reverse transcriptase-polymerase chain reaction, rt-PCR • vasoactive intestinal peptide, VIP This article has been cited by other articles:
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