title: Expression and functions of the duodenal peptide secretin and its receptor in human lung.
abstract: 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.
authors.affiliation: Pharmagene Laboratories, Royston, Hertfordshire, United Kingdom. richard.davis@pharmagene.com
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Davis
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Page
authors.forename: Gabriela J
authors.initials: GJ
authors.lastname: Dos Santos Cruz
authors.forename: Dan W
authors.initials: DW
authors.lastname: Harmer
authors.forename: Peter W
authors.initials: PW
authors.lastname: Munday
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Williams
authors.forename: Joanna
authors.initials: J
authors.lastname: Picot
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Evans
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sheldrick
authors.forename: Robert A
authors.initials: RA
authors.lastname: Coleman
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Clark
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D001993:Bronchodilator Agents / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D012633:Secretin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D001993:Bronchodilator Agents; D018118:Chloride Channels; D002712:Chlorides; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor; D012633:Secretin