Cellular distribution of secretin receptor expression in rat pancreas.
Secretin is an important regulator of pancreatic function, but the molecular basis of its actions is not well understood. We have, therefore, used in situ autoradiography, photoaffinity labeling, and RNase protection assays with healthy rat pancreas, dispersed acinar cells, and pancreas depleted of acinar cells to explore the cellular distribution and molecular identity of high-affinity secretin receptors in this complex organ. The autoradiographic examination of 125I-labeled [Tyr10]rat secretin-27 binding to normal pancreas demonstrated saturable and specific high-affinity binding sites on both acinar and duct cells, with a uniform lobular distribution, but with no binding above background over islets or vascular structures. Photoaffinity labeling demonstrated that the ductular binding site in acinar cell-depleted copper-deficient rat pancreas represented the same glycoprotein with a molecular weight of 50,000-62,000 that was present on acinar cells. RNase protection assays confirmed the molecular identity of the secretin receptors expressed on these distinct cells. The apparent absence or extreme low density of similar secretin receptors on islets and pancreatic vascular structures suggests that the pharmacological effects of secretin on those cells may either be indirect or mediated by another secretin family receptor that recognizes this hormone with lower affinity.
Ulrich
C D
CD
Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0595, USA.
Wood
P
P
Hadac
E M
EM
Kopras
E
E
Whitcomb
D C
DC
Miller
L J
LJ
D000818:Animals; D001345:Autoradiography; D003300:Copper / Q000172:deficiency; D008566:Membranes / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D019920:Photoaffinity Labels; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
D019920:Photoaffinity Labels; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor; D003300:Copper