Expression and functions of the duodenal peptide secretin and its receptor in human lung.
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.
Davis
Richard J
RJ
Pharmagene Laboratories, Royston, Hertfordshire, United Kingdom. richard.davis@pharmagene.com
Page
Keith J
KJ
Dos Santos Cruz
Gabriela J
GJ
Harmer
Dan W
DW
Munday
Peter W
PW
Williams
Sandra J
SJ
Picot
Joanna
J
Evans
Tom J
TJ
Sheldrick
Robert L
RL
Coleman
Robert A
RA
Clark
Kenneth L
KL
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
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