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Developmental differences in the expression of the cholera toxin sensitive subunit (Gs alpha) of adenylate cyclase in the rat small intestine.
  1. I R Sanderson,
  2. Z Xu,
  3. S W Chu,
  4. Q Y Xie,
  5. L J Levine,
  6. W A Walker
  1. Developmental Gastroenterology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, USA.


    BACKGROUND: The stimulatory guanosine triphosphate (GTP) binding protein alpha subunit (Gs alpha) of adenylate cyclase is the target protein for cholera toxin. AIMS/METHODS: The expression of this signal transducer was analysed in the small intestine of developing rats by RNA transfer (northern blot) analysis by immunoblotting, and by ADP-ribosylation of membrane proteins. RESULTS: Intestinal Gs alpha mRNA (about 1.9 kb) was increased in the neonate compared with the adult rat. Two isoforms of Gs alpha proteins, a 45,000 and a 52,000 form, were expressed in the small intestinal epithelial cell and both were ADP-ribosylated by cholera toxin. A significant increase in the larger isoform (52,000) and in its ribosylation was noted in the 2 week old suckling compared with post-weaned older animals. The protein content or ribosylation of the smaller form (45,000) did not significantly change with age. CONCLUSION: These data show that a developmental decline of intestinal Gs alpha expression seems to be, in part, regulated at the mRNA level. An increased Gs alpha expression in the immature intestine may help to explain a previously reported, dose dependent increased adenylate cyclase response and an increase in fluid secretion to cholera toxin in neonates compared with adults.

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