Evidence for and characterization of specific high affinity binding sites for the gastric inhibitory polypeptide in pancreatic beta-cells.
High affinity binding sites have been found in membrane preparations from hamster beta-cell tumors by using radiolabeled gastric inhibitory polypeptide (125I-GIP). HPLC of 125I-GIP resulted in two major peaks (A III and B III), with identical specific binding. It was verified that peaks A III and B III stimulate insulin release from the isolated perfused rat pancreas to an extent at least equal to that obtained with unlabeled GIP at 10(-9) M. Natural GIP competitively inhibited the binding of 125I-GIP in the range of 10(-10) -10(-6) M and half-maximal inhibition was observed at 1.9 +/- 0.19 X 10(-9) M GIP. The number of high affinity sites was 219 +/- 8 fmol/mg protein and the dissociation constant was 2.05 +/- 0.1 X 10(-9) M. None of 10 regulatory peptides tested exhibited any effect on the 125I-GIP binding at concentrations in the range of 10(-6) -10(-4) M. Consequently, saturable, high affinity and specific binding sites for the GIP have been found and characterized in the plasma membranes of beta-cells. This model can be of use in studying the interaction of GIP with its preponderant target tissue.
D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism; D007340:Insulinoma / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000378:metabolism; D013552:Swine; D013696:Temperature; D013997:Time Factors
D005768:Gastrointestinal Hormones; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide