title: GIP(6-30amide) contains the high affinity binding region of GIP and is a potent inhibitor of GIP1-42 action in vitro.
abstract: GIP (Glucose-dependent Insulinotropic Polypeptide) is an important regulator of insulin secretion. The effects of truncated forms of the peptide, GIP(10-30), GIP(6-30amide) and GIP(7-30), on binding of 125I-GIP(1-42) to GIP receptors in transfected CHO-KI cells, and on cyclic AMP responses to GIP(1-42), have been studied with a view to defining further the receptor binding region of GIP, and to establish whether such truncated peptides exhibit agonist or antagonist activity. All three peptides were found to be receptor antagonists, however GIP(6-30amide) exhibited receptor binding affinity equivalent to that of GIP(1-42) in competitive binding studies (IC50 = 3.08+/-0.57 nM). GIP(6-30amide) inhibited GIP(1-42)-induced cAMP production by 58% at a concentration of 100 nM, whereas GIP(10-30) and GIP(7-30), inhibited only in the microM range. GIP(6-30amide) therefore contains the high affinity binding region of GIP and is a potent inhibitor of GIP(1-42) action in vitro.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: R W
authors.initials: RW
authors.lastname: Gelling
authors.forename: D H
authors.initials: DH
authors.lastname: Coy
authors.forename: R A
authors.initials: RA
authors.lastname: Pederson
authors.forename: M B
authors.initials: MB
authors.lastname: Wheeler
authors.forename: S
authors.initials: S
authors.lastname: Hinke
authors.forename: T
authors.initials: T
authors.lastname: Kwan
authors.forename: C H
authors.initials: CH
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D005749:Gastric Inhibitory Polypeptide / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D010446:Peptide Fragments; D011964:Receptors, Gastrointestinal Hormone; C101760:gastric inhibitory polypeptide (1-42); D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor; D000242:Cyclic AMP