Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Jun;83(12):4355–4359. doi: 10.1073/pnas.83.12.4355

Evidence for a common evolutionary origin of brain and pancreas cholecystokinin receptors.

S R Vigna, M C Thorndyke, J A Williams
PMCID: PMC323731  PMID: 3012565

Abstract

An evolutionary basis for the distinct forms of cholecystokinin (CCK) receptors in the mammalian brain and pancreas was examined. The brains and pancreases of ratfish, frog, snake, and chicken contained saturable, high-affinity binding sites for iodinated porcine CCK-33. In the ectothermic species, the brain and pancreas CCK receptors exhibited nearly the same relative specificities for various CCKs and gastrins. Sulfated CCK-8 and sulfated gastrin-17 were the most potent while their nonsulfated analogs and gastrin-4 were less potent. By contrast, in the chicken, the specificities of brain and pancreas CCK receptors closely resembled their mammalian counterparts. We conclude that brain and pancreas CCK receptors with new specificities for binding CCKs and gastrins evolved at the level of the divergence of endotherms (birds and mammals) from reptiles. We propose that the prior evolution of gastrin provided the selection pressure for these changes. The endotherm pancreas receptor arose in evolution by narrowing its requirement for the position of a sulfated tyrosine residue in its ligands from either the sixth or seventh position from the carboxyl terminus to the seventh position only. The endotherm brain receptor arose in evolution by losing its requirement for a sulfated ligand and by transferring its high-affinity binding domain from the tyrosine residue in the carboxyl termini of CCK and gastrin to the carboxyl-terminal tetrapeptide active site common to CCKs and gastrins.

Full text

PDF
4355

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bergland R. M., Page R. B. Pituitary-brain vascular relations: a new paradigm. Science. 1979 Apr 6;204(4388):18–24. doi: 10.1126/science.373118. [DOI] [PubMed] [Google Scholar]
  2. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  3. GREGORY R. A., TRACY H. J. A NOTE ON THE NATURE OF THE GASTRIN-LIKE STIMULANT PRESENT IN ZOLLINGER-ELLISON TUMOURS. Gut. 1964 Apr;5:115–117. [PubMed] [Google Scholar]
  4. Gaudreau P., Quirion R., St-Pierre S., Pert C. B. Characterization and visualization of cholecystokinin receptors in rat brain using [3H]pentagastrin. Peptides. 1983 Sep-Oct;4(5):755–762. doi: 10.1016/0196-9781(83)90032-3. [DOI] [PubMed] [Google Scholar]
  5. Innis R. B., Snyder S. H. Distinct cholecystokinin receptors in brain and pancreas. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6917–6921. doi: 10.1073/pnas.77.11.6917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Jensen R. T., Lemp G. F., Gardner J. D. Interaction of cholecystokinin with specific membrane receptors on pancreatic acinar cells. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2079–2083. doi: 10.1073/pnas.77.4.2079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Larsson L. I., Rehfeld J. F. Evidence for a common evolutionary origin of gastrin and cholecystokinin. Nature. 1977 Sep 22;269(5626):335–338. doi: 10.1038/269335a0. [DOI] [PubMed] [Google Scholar]
  8. Larsson L. I., Rehfeld J. F. Pituitary gastrins occur in corticotrophs and melanotrophs. Science. 1981 Aug 14;213(4509):768–770. doi: 10.1126/science.6266012. [DOI] [PubMed] [Google Scholar]
  9. Lee R. W., Huttner W. B. Tyrosine-O-sulfated proteins of PC12 pheochromocytoma cells and their sulfation by a tyrosylprotein sulfotransferase. J Biol Chem. 1983 Sep 25;258(18):11326–11334. [PubMed] [Google Scholar]
  10. Miller L. J., Rosenzweig S. A., Jamieson J. D. Preparation and characterization of a probe for the cholecystokinin octapeptide receptor, N alpha (125I-desaminotyrosyl)CCK-8, and its interactions with pancreatic acini. J Biol Chem. 1981 Dec 10;256(23):12417–12423. [PubMed] [Google Scholar]
  11. Rehfeld J. F., Kruse-Larsen C. Gastrin and cholecystokinin in human cerebrospinal fluid. Immunochemical determination of concentrations and molecular heterogeneity. Brain Res. 1978 Oct 20;155(1):19–26. doi: 10.1016/0006-8993(78)90301-3. [DOI] [PubMed] [Google Scholar]
  12. Rehfeld J. F. Localisation of gastrins to neuro- and adenohypophysis. Nature. 1978 Feb 23;271(5647):771–773. doi: 10.1038/271771a0. [DOI] [PubMed] [Google Scholar]
  13. Saito A., Goldfine I. D., Williams J. A. Characterization of receptors for cholecystokinin and related peptides in mouse cerebral cortex. J Neurochem. 1981 Aug;37(2):483–490. doi: 10.1111/j.1471-4159.1981.tb00481.x. [DOI] [PubMed] [Google Scholar]
  14. Saito A., Sankaran H., Goldfine I. D., Williams J. A. Cholecystokinin receptors in the brain: characterization and distribution. Science. 1980 Jun 6;208(4448):1155–1156. doi: 10.1126/science.6246582. [DOI] [PubMed] [Google Scholar]
  15. Sakamoto C., Williams J. A., Goldfine I. D. Brain CCK receptors are structurally distinct from pancreas CCK receptors. Biochem Biophys Res Commun. 1984 Oct 30;124(2):497–502. doi: 10.1016/0006-291x(84)91581-x. [DOI] [PubMed] [Google Scholar]
  16. Sankaran H., Deveney C. W., Goldfine I. D., Williams J. A. Preparation of biologically active radioiodinated cholecystokinin for radioreceptor assay and radioimmunoassay. J Biol Chem. 1979 Oct 10;254(19):9349–9351. [PubMed] [Google Scholar]
  17. Sankaran H., Goldfine I. D., Deveney C. W., Wong K. Y., Williams J. A. Binding of cholecystokinin to high affinity receptors on isolated rat pancreatic acini. J Biol Chem. 1980 Mar 10;255(5):1849–1853. [PubMed] [Google Scholar]
  18. Steigerwalt R. W., Williams J. A. Characterization of cholecystokinin receptors on rat pancreatic membranes. Endocrinology. 1981 Nov;109(5):1746–1753. doi: 10.1210/endo-109-5-1746. [DOI] [PubMed] [Google Scholar]
  19. Vigna S. R., Steigerwalt R. W., Williams J. A. Characterization of cholecystokinin receptors in bullfrog (Rana catesbeiana) brain and pancreas. Regul Pept. 1984 Oct;9(3):199–212. doi: 10.1016/0167-0115(84)90072-7. [DOI] [PubMed] [Google Scholar]
  20. Williams J. A., Vigna S. R., Sakamoto C., Goldfine I. D. Brain cholecystokinin receptors. Binding characteristics, covalent cross-linking, and evolutionary aspects. Ann N Y Acad Sci. 1985;448:220–230. doi: 10.1111/j.1749-6632.1985.tb29920.x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES