cAMP increases junctional conductance and stimulates phosphorylation of the 27-kDa principal gap junction polypeptide

J. C. Saez, D. C. Spray, A. C. Nairn, E. Hertzberg, P. Greengard, M. V. Bennett

Research output: Contribution to journalArticle

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Abstract

Membrane-permeant cAMP derivatives (dibutyryl- and 8-bromo-cAMP) increase gap-junctional conductance within minutes when applied to voltage-clamped pairs of rat hepatocytes. Glucagon also increases junctional conductances, but the response has a more rapid onset and is more rapidly reversible. The glucagon effect can be prevented by intracellular injection of the protein inhibitor of the cAMP-dependent protein kinase (Walsh inhibitor), indicating that the catalytic subunit of cAMP-dependent protein kinase is directly involved. The 27-kDa major gap junction polypeptide is phosphorylated when liver cells dissociated into small groups are incubated with 32P. Addition of 8-bromo-cAMP to cells increases the incorporation of 32P into the 27-kDa junctional protein. Serine is the amino acid residue that is phosphorylated. When isolated liver gap junctions are incubated in the presence of catalytic subunit of the cAMP-dependent protein kinase, the 27-kDa gap junction polypeptide is phosphorylated with low stoichiometry on serine. The rapid increases in gap junctional conductance caused by agents that elevate cAMP and phosphorylation of the gap junction protein by cAMP-dependent protein kinase suggest that cAMP-dependent phosphorylation of the gap junction channel modulates the conductance of liver gap junctions.

Original languageEnglish (US)
Pages (from-to)2473-2477
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume83
Issue number8
StatePublished - 1986

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Gap Junctions
Cyclic AMP-Dependent Protein Kinases
Phosphorylation
Peptides
8-Bromo Cyclic Adenosine Monophosphate
Glucagon
Serine
Liver
Catalytic Domain
Connexins
Protein Kinase Inhibitors
Hepatocytes
Proteins
Amino Acids
Injections
Membranes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

cAMP increases junctional conductance and stimulates phosphorylation of the 27-kDa principal gap junction polypeptide. / Saez, J. C.; Spray, D. C.; Nairn, A. C.; Hertzberg, E.; Greengard, P.; Bennett, M. V.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 83, No. 8, 1986, p. 2473-2477.

Research output: Contribution to journalArticle

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T1 - cAMP increases junctional conductance and stimulates phosphorylation of the 27-kDa principal gap junction polypeptide

AU - Saez, J. C.

AU - Spray, D. C.

AU - Nairn, A. C.

AU - Hertzberg, E.

AU - Greengard, P.

AU - Bennett, M. V.

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N2 - Membrane-permeant cAMP derivatives (dibutyryl- and 8-bromo-cAMP) increase gap-junctional conductance within minutes when applied to voltage-clamped pairs of rat hepatocytes. Glucagon also increases junctional conductances, but the response has a more rapid onset and is more rapidly reversible. The glucagon effect can be prevented by intracellular injection of the protein inhibitor of the cAMP-dependent protein kinase (Walsh inhibitor), indicating that the catalytic subunit of cAMP-dependent protein kinase is directly involved. The 27-kDa major gap junction polypeptide is phosphorylated when liver cells dissociated into small groups are incubated with 32P. Addition of 8-bromo-cAMP to cells increases the incorporation of 32P into the 27-kDa junctional protein. Serine is the amino acid residue that is phosphorylated. When isolated liver gap junctions are incubated in the presence of catalytic subunit of the cAMP-dependent protein kinase, the 27-kDa gap junction polypeptide is phosphorylated with low stoichiometry on serine. The rapid increases in gap junctional conductance caused by agents that elevate cAMP and phosphorylation of the gap junction protein by cAMP-dependent protein kinase suggest that cAMP-dependent phosphorylation of the gap junction channel modulates the conductance of liver gap junctions.

AB - Membrane-permeant cAMP derivatives (dibutyryl- and 8-bromo-cAMP) increase gap-junctional conductance within minutes when applied to voltage-clamped pairs of rat hepatocytes. Glucagon also increases junctional conductances, but the response has a more rapid onset and is more rapidly reversible. The glucagon effect can be prevented by intracellular injection of the protein inhibitor of the cAMP-dependent protein kinase (Walsh inhibitor), indicating that the catalytic subunit of cAMP-dependent protein kinase is directly involved. The 27-kDa major gap junction polypeptide is phosphorylated when liver cells dissociated into small groups are incubated with 32P. Addition of 8-bromo-cAMP to cells increases the incorporation of 32P into the 27-kDa junctional protein. Serine is the amino acid residue that is phosphorylated. When isolated liver gap junctions are incubated in the presence of catalytic subunit of the cAMP-dependent protein kinase, the 27-kDa gap junction polypeptide is phosphorylated with low stoichiometry on serine. The rapid increases in gap junctional conductance caused by agents that elevate cAMP and phosphorylation of the gap junction protein by cAMP-dependent protein kinase suggest that cAMP-dependent phosphorylation of the gap junction channel modulates the conductance of liver gap junctions.

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