Importance of sulfation of gastrin or cholecystokinin (CCK) on affinity for gastrin and CCK receptors

• Published in: Peptides (New York, N.Y. : 1980) Vol. 10; no. 4; pp. 785 - 789
• Main Authors: Huang, S.C, Yu, D.-H, Wank, S.A, Mantey, S, Gardner, J.D, Jensen, R.T
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.1989; Elsevier Science
• Subjects: 550201 - Biochemistry- Tracer Techniques; AFFINITY; AMYLASE; Amylases - metabolism; ANIMALS; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BIOCHEMICAL REACTION KINETICS; Biological and medical sciences; BODY; Cholecystokinin - metabolism; DAYS LIVING RADIOISOTOPES; DIGESTIVE SYSTEM; ELECTRON CAPTURE RADIOISOTOPES; ENDOCRINE GLANDS; Endocrine pancreas; ENZYMES; Fundamental and applied biological sciences. Psychology; GASTRIN; Gastrins - metabolism; GLANDS; GLYCOSYL HYDROLASES; GUINEA PIGS; HORMONES; Hormones. Régulation; HYDROLASES; IN VITRO; In Vitro Techniques; INTERMEDIATE MASS NUCLEI; IODINE 125; IODINE ISOTOPES; Iodine Radioisotopes; ISOTOPE APPLICATIONS; ISOTOPES; KINETICS; KININS; Male; MAMMALS; MEMBRANE PROTEINS; NUCLEI; O-GLYCOSYL HYDROLASES; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANS; OXYGEN COMPOUNDS; PANCREAS; Pancreas - enzymology; Pancreas - metabolism; Pancreatic acini; PEPTIDE HORMONES; PEPTIDES; POLYPEPTIDES; PROTEINS; RADIOISOTOPES; REACTION KINETICS; Receptor affinity; RECEPTORS; Receptors, Cholecystokinin - metabolism; RODENTS; Sincalide - analogs & derivatives; Sincalide - metabolism; Succinimides - metabolism; SULFATES; Sulfates - metabolism; Sulfation; SULFUR COMPOUNDS; TRACER TECHNIQUES; VERTEBRATES; Vertebrates: endocrinology; Receptor affinity; Pancreatic acini; Sulfation; Rodentia; Peptide hormone; Neuropeptide; Biological activity; Sulfatation; Vertebrata; Mammalia; Guinea pig; Gastrointestinal hormone; Gastrin; Cholecystokinin; Endocrine pancreas; Hormonal receptor
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/0196-9781(89)90114-9

We investigated the importance of sulfation of gastrin or cholecystokinin (CCK) on influencing their affinity for gastrin or CCK receptors by comparing the abilities of sulfated gastrin-17 (gastrin-17-II), desulfated gastrin-17 (gastrin-17-I), CCK-8 and desulfated CCK-8 [des(SO 3)CCK-8] to interact with CCK or gastrin receptors on guinea pig pancreatic acini. For inhibiting binding of 125I-gastrin to gastrin receptors, gastrin-17-II (K d 0.08 nM) > CCK-8 (K d 0.4 nM) > gastrin-17-I (K d 1.5 nM) > des(SO 3)CCK-8 (K d 28 nM). For inhibiting binding of 125I-Bolton Hunter-labeled CCK-8 to CCK receptors the relative potencies were: CCK-8 ⪢ des(SO 3)CCK-8 = gastrin-17-II > gastrin-17-I. Each peptide interacted with both high and low affinity CCK binding sites. The relative abilities of each peptide to interact with high affinity CCK receptors showed a close correlation with their abilities to cause half-maximal stimulation of enzyme secretion. These results demonstrate that, in contrast to older studies, sulfation of both CCK and gastrin increase their affinities for both gastrin and CCK receptors. Moreover, the gastrin receptor is relatively insensitive to the position of the sulfate moiety, whereas the CCK receptor is extremely sensitive to both the presence and exact position of the sulfate moiety.