AJP - Endocrinology and Metabolism, Vol 258, Issue 4 E562-E568, Copyright © 1990 by American Physiological Society
Regulatory effect of cholecystokinin on subsequent insulin binding to pancreatic acini
Y. Okabayashi, M. Otsuki, T. Nakamura, M. Koide, H. Hasegawa, T. Okutani and Y. Kido
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
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)
