Characterization of cholecystokinin receptors and messenger RNA expression in rat pancreas: evidence for expression of cholecystokinin-A receptors but not cholecystokinin-B (gastrin) receptors.
It has been previously demonstrated that guinea pig pancreas possesses both cholecystokinin-A (CCK-A) receptors and CCK-B (gastrin) receptors. In contrast to guinea pig pancreas, it is not known whether CCK receptors in rat pancreas are CCK-A receptors, CCK-B (gastrin) receptors, or both. Thus, in the present study, we characterized CCK receptors in rat pancreas at the receptor and mRNA level. 125I-Bolton-Hunter-labeled CCK octapeptide (125I-BH-CCK-8), the specific CCK-A and CCK-B (gastrin) receptor antagonists L364,718 and L365,260, and 125I-labeled gastrin-I were utilized to characterize CCK receptors in normal rat pancreas. Additionally, we utilized 32P-labeled cDNA probes of the CCK-A receptor and CCK-B (gastrin) receptor coding regions in order to examine the expression of CCK receptor subtypes in normal rat pancreas at the mRNA level. The dose-inhibition curve of CCK-8 inhibiting binding of 125I-BH-CCK-8 was significantly best fit by a two-site model with a high-affinity site (Kd = 0.68 +/- 0.13 nM) and a low-affinity site (Kd = 656 +/- 289 nM). L364,718 inhibited binding of 125I-BH-CCK-8 with high affinity, whereas no high-affinity inhibition for L365,260 to inhibit binding of 125I-BH-CCK-8 was detected. L364,718 was 627 times as potent as L365,260 in inhibiting binding of 125I-BH-CCK-8. No saturable binding was present for 125I-labeled gastrin-I. Gastrin-17-I did not inhibit binding of 125I-BH-CCK-8.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhou
W
W
Department of Surgery, University of Cincinnati College of Medicine, Ohio.
Povoski
S P
SP
Bell
R H
RH
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015870:Gene Expression; D008297:Male; D008969:Molecular Sequence Data; D010179:Pancreas / Q000737:chemistry / Q000378:metabolism*; D010190:Pancreatic Neoplasms; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D012194:RNA-Directed DNA Polymerase; D051381:Rats; D011917:Rats, Inbred Lew; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000235:genetics* / Q000378:metabolism; D012844:Sincalide / Q000031:analogs & derivatives / Q000378:metabolism; D013388:Succinimides / Q000378:metabolism; D014407:Tumor Cells, Cultured
C044758:Bolton Hunter-cholecystokinin octapeptide; D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D013388:Succinimides; D012194:RNA-Directed DNA Polymerase; D012844:Sincalide