Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1973 Aug;52(8):2053–2059. doi: 10.1172/JCI107389

Development of Intestinal Adenyl Cyclase and Its Response to Cholera Enterotoxin

Richard J Grand 1,2, Frank M Torti 1,2, Stephanie Jaksina 1,2
PMCID: PMC302487  PMID: 4352579

Abstract

Adenyl cyclase activity in intestinal membranes has been studied during development in the rabbit fetus from fetal day 17 to 10 days postnatally and in the human fetus from the 10th to the 17th wk of gestation. In the rabbit, the enzyme was already present by fetal day 17 and showed a fourfold peak rise in specific activity by 22 days. By 28 days, the specific activity had fallen toward adult levels and remained constant throughout gestation and the 1st wk of life. Fluoridestimulated activity showed a similar curve, and was 2.5-5 times the basal values. Activities in jejunum and ileum were comparable at all time points studied. Phosphodiesterase activity did not change during gestation. When fetal intestinal segments were incubated in vitro with purified cholera enterotoxin, adenyl cyclase activity in subsequently prepared membranes was increased two- to threefold. This level was not regularly further elevated by fluoride ion. Lithium ion inhibited both the basal and fluoride-stimulated enzyme activity in membranes prepared from rabbit fetuses at term. Lactase activity (reflecting the development of the microvilli) in either whole intestinal homogenates or in the membrane fractions showed a differnet pattern of development, with a rise beginning on fetal day 24 and a plateau just after birth. In intestinal membranes prepared from human fetuses, the activity of both basal and fluoride-stimulated adenyl cyclase tripled from the 10th to the 17th wk of gestation. The data both in the rabbit and in man show that intestinal adenyl cyclase is capable of responding to cholera enterotoxin quite early in gestation. In the rabbit, this occurs before the time of appearance or ville or of an enzyme marker (lactase) for microville. The results support the concept that adenyl cyclase is present in plasma membrane other than the brush border.

Full text

PDF
2053

Selected References

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

  1. Birnbaumer L., Pohl S. L., Rodbell M. Adenyl cyclase in fat cells. 1. Properties and the effects of adrenocorticotropin and fluoride. J Biol Chem. 1969 Jul 10;244(13):3468–3476. [PubMed] [Google Scholar]
  2. Bär H. P., Hahn P. Development of rat liver adenylcyclase. Can J Biochem. 1971 Jan;49(1):85–89. doi: 10.1139/o71-013. [DOI] [PubMed] [Google Scholar]
  3. Carpenter C. C., Jr, Hirschhorn N. Pediatric cholera: current concepts of therapy. J Pediatr. 1972 May;80(5):874–878. [PubMed] [Google Scholar]
  4. Chen L. C., Rohde J. E., Sharp G. W. Properties of adenyl cyclase from human jejunal mucosa during naturally acquired cholera and convalescence. J Clin Invest. 1972 Apr;51(4):731–740. doi: 10.1172/JCI106867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DOELL R. G., KRETCHMER N. Studies of small intestine during development. I. Distribution and activity of beta-galactosidase. Biochim Biophys Acta. 1962 Aug 13;62:353–362. doi: 10.1016/0006-3002(62)90097-5. [DOI] [PubMed] [Google Scholar]
  6. Dahlqvist A., Lindberg T. Development of the intestinal disaccharidase and alkaline phosphatase activities in the human foetus. Clin Sci. 1966 Jun;30(3):517–528. [PubMed] [Google Scholar]
  7. Dean A. G., Ching Y. C., Williams R. G., Harden L. B. Test for Escherichia coli enterotoxin using infant mice: application in a study of diarrhea in children in Honolulu. J Infect Dis. 1972 Apr;125(4):407–411. doi: 10.1093/infdis/125.4.407. [DOI] [PubMed] [Google Scholar]
  8. Deren J. J., Strauss E. W., Wilson T. H. The development of structure and transport systems of the fetal rabbit intestine. Dev Biol. 1965 Dec;12(3):467–486. doi: 10.1016/0012-1606(65)90010-2. [DOI] [PubMed] [Google Scholar]
  9. Evans D. J., Jr, Chen L. C., Curlin G. T., Evans D. G. Stimulation of adenyl cyclase by Escherichia coli enterotoxin. Nat New Biol. 1972 Apr 5;236(66):137–138. doi: 10.1038/newbio236137a0. [DOI] [PubMed] [Google Scholar]
  10. Field M: Intestinal secretion: effect of cyclic AMP and its role in cholera. N Engl J Med. 1971 May 20;284(20):1137–1144. doi: 10.1056/NEJM197105202842008. [DOI] [PubMed] [Google Scholar]
  11. Field M., Fromm D., al-Awqati Q., Greenough W. B., 3rd Effect of cholera enterotoxin on ion transport across isolated ileal mucosa. J Clin Invest. 1972 Apr;51(4):796–804. doi: 10.1172/JCI106874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gilman A. G. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. doi: 10.1073/pnas.67.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gorbach S. L., Khurana C. M. Toxigenic Escherichia coli: a cause of infantile diarrhea in Chicago. N Engl J Med. 1972 Oct 19;287(16):791–795. doi: 10.1056/NEJM197210192871603. [DOI] [PubMed] [Google Scholar]
  14. Grand R. J., Chong D. A., Isselbacher K. J. Intracellular processing of disaccharidases: the effect of actinomycin D. Biochim Biophys Acta. 1971 Feb 28;261(2):341–352. doi: 10.1016/0304-4165(72)90058-x. [DOI] [PubMed] [Google Scholar]
  15. Hermos J. A., Mathan M., Trier J. S. DNA synthesis and proliferation by villous epithelial cells in fetal rats. J Cell Biol. 1971 Jul;50(1):255–258. doi: 10.1083/jcb.50.1.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hommes F. A., Beere A. The development of adenyl cyclase in rat liver, kidney, brain and skeletal muscle. Biochim Biophys Acta. 1971 May 18;237(2):296–300. doi: 10.1016/0304-4165(71)90321-7. [DOI] [PubMed] [Google Scholar]
  17. Kimberg D. V., Field M., Johnson J., Henderson A., Gershon E. Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and prostaglandins. J Clin Invest. 1971 Jun;50(6):1218–1230. doi: 10.1172/JCI106599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  19. Messer M., Dahlqvist A. A one-step ultramicro method for the assay of intestinal disaccharidases. Anal Biochem. 1966 Mar;14(3):376–392. doi: 10.1016/0003-2697(66)90280-6. [DOI] [PubMed] [Google Scholar]
  20. Mosley W. H., Benenson A. S., Barui R. A serological survey for cholear antibodies in rural east Pakistan. 1. The distribution of antibody in the control population of a cholera-vaccine field-trial area and the relation of antibody titre to the pattern of endemic cholera. Bull World Health Organ. 1968;38(3):327–334. [PMC free article] [PubMed] [Google Scholar]
  21. Parkinson D. K., Ebel H., DiBona D. R., Sharp G. W. Localization of the action of cholera toxin on adenyl cyclase in mucosal epithelial cells of rabbit intestine. J Clin Invest. 1972 Sep;51(9):2292–2298. doi: 10.1172/JCI107039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pierce N. F., Wallace C. K. Stimulation of jejunal secretion by a crude Escherichia coli enterotixin. Gastroenterology. 1972 Sep;63(6):439–448. [PubMed] [Google Scholar]
  23. Schafer D. E., Lust W. D., Sircar B., Goldberg N. D. Elevated concentration of adenosine 3':5'-cyclic monophosphate in intestinal mucosa after treatment with cholera toxin. Proc Natl Acad Sci U S A. 1970 Oct;67(2):851–856. doi: 10.1073/pnas.67.2.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schmidt M. J., Palmer E. C., Dettbarn W. D., Robison G. A. Cyclic AMP and adenyl cyclase in the developing rat brain. Dev Psychobiol. 1970;3(1):53–67. doi: 10.1002/dev.420030108. [DOI] [PubMed] [Google Scholar]
  25. Schou M., Amdisen A., Thomsen K. Clinical and experimental observations concerning the absorption and elimination of lithium and on lithium poisoning. Acta Psychiatr Scand Suppl. 1968;203:153–155. doi: 10.1111/j.1600-0447.1968.tb01983.x. [DOI] [PubMed] [Google Scholar]
  26. Sharp G. W., Hynie S. Stimulation of intestinal adenyl cyclase by cholera toxin. Nature. 1971 Jan 22;229(5282):266–269. doi: 10.1038/229266a0. [DOI] [PubMed] [Google Scholar]
  27. Wolff J., Berens S. C., Jones A. B. Inhibition of thyrotropin-stimulated adenyl cyclase activity of beef thyroid membranes by low concentration of lithium ion. Biochem Biophys Res Commun. 1970 Apr 8;39(1):77–82. doi: 10.1016/0006-291x(70)90760-6. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES