title: Regulatory effect of cholecystokinin on subsequent insulin binding to pancreatic acini.
abstract: We investigated the regulatory effect of cholecystokinin (CCK) on subsequent insulin binding to pancreatic acinar cells. Rat isolated acini were preincubated with various concentrations of CCK octapeptide (CCK-8) at 37 degrees C. Acini were then washed, resuspended in the binding buffer, and incubated with 8.3 pM 125I-labeled insulin for 60 min at 37 degrees C. Pretreatment with CCK-8 caused inhibition of subsequent 125I-insulin binding that was time and concentration dependent. Significant inhibition was observed with 3 pM CCK-8. Computer analysis of the competition-inhibition study with a nonlinear least-squares curve-fitting program revealed that CCK-8 pretreatment of acini reduced the receptor affinity of the high-affinity binding site. This inhibitory action of CCK-8 was not due to the alteration in degradation or internalization of the tracer. When acini were pretreated with 100 pM CCK-8 for 120 min at 4 degrees C, a reduction in the receptor affinity of the high-affinity binding site was also observed. In pancreatic membrane prepared from acini preincubated with 100 pM CCK-8 for 120 min at 37 degrees C, displacement of 125I-insulin (83 pM) by unlabeled insulin (24 degrees C, 1 h) revealed that CCK-8 inhibited 125I-insulin binding by altering the receptor affinity of the high-affinity binding site. In acinar preparations the inhibitory effect of CCK-8 on 125I-insulin binding was abolished when acini were preincubated with CCK-8 and CCK receptor antagonist L 374718 at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okabayashi
authors.forename: M
authors.initials: M
authors.lastname: Otsuki
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Koide
authors.forename: H
authors.initials: H
authors.lastname: Hasegawa
authors.forename: T
authors.initials: T
authors.lastname: Okutani
authors.forename: Y
authors.initials: Y
authors.lastname: Kido
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D000001:Calcimycin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D007328:Insulin; D000001:Calcimycin; D002217:Carbachol; D011972:Receptor, Insulin; D012844:Sincalide; D013755:Tetradecanoylphorbol Acetate