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Modulation of adenylate cyclase activity by Ca2+, phospholipid-dependent protein kinase in rat brain striatum

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Summary

The effects of purified Ca2+, phospholipid-dependent protein kinase (C-kinase) were studied on adenylate cyclase activity from rat brain striatum. C-kinase treatment of the membranes stimulated adenylate cyclase activity, the maximal stimulation between 50–80% was observed at 3.5 U/ml, whereas the catalytic subunit of cAMP dependent protein kinase did not show any effect on enzyme activity. The inclusion of Ca2+ and phosphatidyl serine did not augment the percent stimulation of adenylate cyclase by C-kinase, however EGTA inhibited the stimulatory effect of C-kinase on enzyme activity. Furthermore, the known inhibitors of C-kinase such as polymyxin-B and 1-(5-Isoquinoline sulfonyl)-2-methylpiperazine dihydrochloride (H-7) also inhibited the stimulatory effect of C-kinase on adenylate cyclase activity. In addition, in the presence of GTP the stimulatory effects of C-kinase on basal and N-Ethylcarboxamide adenosine- (NECA-), dopamine-(DA) and forskolin- (FSK) sensitive adenylate cyclase activities were augmented. On the other hand, the inhibitory effect of high concentrations of GTP on enzyme activity was attenuated by C-kinase treatment. In addition, oxotremorine inhibited adenylate cyclase activity in a concentration dependent manner, with an apparent Ki of about 10 µM and C-kinase treatment almost completely abolished this inhibition. These data suggest that C-kinase may play an important role in the regulation of adenylate cyclase activity possibly by interacting with a guanine nucleotide regulatory protein.

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Abbreviations

C-kinase:

Ca2− phospholipid-dependent protein kinase

NECA:

N-Ethylcarboxamide adenosine

DA:

Dopamine

FSK:

Forskolin

PMA:

Phorbol 12-(-Myristate), 13-Acetate, H-7, 1-(5-isoquinoline sulfonyl)-2-methylpiperazine dihydrochloride

References

  1. Heisler S: 12–0-Tetradecanoyl-phorbol-13-acetate-induced secretion in pituitary tumor cells. Eur J Pharmacol 98: 177–183,1984

    Google Scholar 

  2. Brostrom MA, Brostrom CO, Brotman LA, Lee CS, Wolff DJ, Gelley HM: Alterations of glial tumor cell Ca2+ metabolism and Ca2+-dependent cAMP accumulation by phorbol myristate acetate. J Biol Chem 257: 6758–6765, 1982

    Google Scholar 

  3. Heyworth CM, Whetton AD, Kinsella AR, Honslay MD: The phorbol ester, TPA inhibits glucagon-stimulated adenylate cyclase activity. FEBS Lett 170: 38–42, 1984

    Google Scholar 

  4. Mukhopadhyay AK, Schumacher M: Inhibition of hCG-stimulated adenylate cyclase in purified mouse Leydig cells by the phorbol ester PMA. FEBS Lett 187: 56–60, 1985

    Google Scholar 

  5. Jakobs KH, Bauer S, Watanabe Y: Modulation of adenylate cyclase of human platelets by phorbol ester: impairment of hormone-sensitive inhibitory pathway. Eur J Biochem 151: 425–430, 1985

    Google Scholar 

  6. Perchellet JP, Boutwell RK: Enhancement by 3-isobutyl-1-methylxanthine and cholera toxin of 12–0-tetradecanoylphorbol-13-acetate-stimulated cyclic nucleotide levels and ornithine decarboxylase activity in isolated epidermal cells. Cancer Res 40: 2653–2660, 1980

    Google Scholar 

  7. Simanton R, Sachs L: Enhancement of hormone action by a phorbol ester and anti-tubulin alkaloids involves different mechanisms. Biochim Biophys Acta 720: 120–125, 1982

    Google Scholar 

  8. Bell JD, Buxton IL, Brunton LLL: Enhancement of adenylate cyclase activity in S49 lymphoma cells by phorbol ester. Putative effect of C-kinase on αs-GTP-ctalytic subunit interaction. J Biol Chem 260: 2625–2628, 1985

    Google Scholar 

  9. Anand-Srivastava MB: Differential effects of phorbol ester on adenylate cyclase from brain striatum and anterior pituitary. Fed Proc 44: 696, 1985

    Google Scholar 

  10. Nambi P, Sibley DR, Lefkowitz RJ: Desensitization of frog erythrocyte adenylate cyclase system by tumor-promoting phorbol esters. Can J Physiol Pharmacol 63: 983–986, 1985

    Google Scholar 

  11. Castagna M, Takai Y, Kaibuch K, Sano K, Kikkawa U, Nishizuka Y: Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem 257: 7847–7851, 1982

    Google Scholar 

  12. Niedel J, Kuhn LJ, Vanderbark GR: Phorbol diester receptor copurifies with protein kinase C. Proc Natl Acad Sci USA 80: 36–40, 1983

    Google Scholar 

  13. Katada T, Gilman AH, Watanabe Y, Bauer S, Jakobs KH: Protein kinase C phosphorylates the inhibitory guanine nucleotide-binding regulatory component and apparently suppresses its functions in hormonal inhibition of adenylate cyclase. Eur J Biochem 151: 431–437, 1985

    Google Scholar 

  14. Cochet C, Gill GN, Meisenhelder J, Cooper JA, Hunter T: C-kinase phosphorylates the epidermal growth factor receptor and reduced its epidermal growth factor-stimulated tyrosine protein kinase activity. J Biol Chem 259: 2553–2558,1984

    Google Scholar 

  15. Woodgett JR, Hunter T: Isolation and characterization of two distinct forms of protein kinase C. J Biol Chem 262: 4836–4843,1987

    Google Scholar 

  16. Srivastava AK, Waisman DM, Brostrom CO, Soderling TR: Stimulation of glycogen synthase phosphorylation by calcium dependent regulator protein. J Biol Chem 254: 583–586,1979

    Google Scholar 

  17. Anand-Srivastava MB, Johnson RA: Regulation of adenosine-sensitive adenylate cyclase from rat brain striatum. J Neurochem 35: 905–914,1980

    Google Scholar 

  18. Anand-Srivastava MB: Regulation of adenylate cyclase by adenosine and other agonists in rat myocardial sarcolemma. Arch Biochem Biophys 243: 439–446, 1985

    Google Scholar 

  19. Salomon Y, Londos C, Rodbell M: A highly sensitive adenylate cyclase assay. Anal Biochem 58: 541–545, 1974

    Google Scholar 

  20. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275, 1951

    CAS  PubMed  Google Scholar 

  21. Kawamoto S, Hidaka H: 1-(5-isoquinoline sulfonyl)-2-methyl piperazine (H-7) is a selective inhibitor of protein kinase C in rabbit platelets. Biochem Biophys Res Commun 125:258–264,1984

    Google Scholar 

  22. Olianas MC, Onali P, Neff NH, Costa E: Adenylate cyclase activity of synaptic membranes from rat striatum. Inhibition by muscarinic receptor agonists. Mol Pharmacol 23: 393–398,1983

    Google Scholar 

  23. Anand-Srivastava MB, Johnson RA: Role of phospholipids in coupling of adenosine and dopamine receptors to striatal adenylate cyclase. J Neurochem 36: 1819–1828, 1981

    Google Scholar 

  24. Sibley DR, Jeff RA, Daniel K, Nambi P, Lefkowitz RJ: Phorbol diester treatment promotes enhanced adenylate cyclase activity in frog erythrocytes. Arch Biochem Biophys 244: 373–381, 1986

    Google Scholar 

  25. Naghshineh S, Noguchi M, Huang K-P, Londos C: Activation of adipocyte adenylate cyclase by protein kinase C. J Biol Chem 261: 14534–14538, 1986

    Google Scholar 

  26. Yoshimasa T, Sibley DR, Bouvier M, Lefkowitz RJ, Caron MG: Crosstalk between cellular signalling pathways suggested by phorbol ester induced adenylate cyclase phosphorylation. Nature 327: 67–70, 1987

    Google Scholar 

  27. Katada T, Ui M: ADP-ribosylation of the specific membrane protein of C6 cells by islet-activating protein associated with modification of adenylate cyclase activity. J Biol Chem 257: 7210–7216, 1982

    Google Scholar 

  28. Anand-Srivastava MB, Srivastava AK, Cantin M: Pertussis toxin attenuates atrial natriuretic factor-mediated inhibition of adenylate cyclase: involvement of inhibitory gua nine nucleotide regulatory protein. J Biol Chem 262: 4931–4934,1987

    Google Scholar 

  29. Watanabe Y, Horn F, Bauer S, Jakobs KH: Protein kinase C interferes with Ni-mediated inhibition of human platelet adenylate cyclase. FEBS Lett 192: 23–27, 1985

    Google Scholar 

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Authors and Affiliations

  1. Clinical Research Institute of Montreal, 110 Pine Avenue West, H2W IR7, Montreal, Quebec, Canada

    Madhu B. Anand-Srivastava & Ashok K. Srivastava

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  1. Madhu B. Anand-Srivastava
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  2. Ashok K. Srivastava
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Additional information

M.B.A.-S. was Canadian Heart Foundation Scholar during the course of these studies.

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Anand-Srivastava, M.B., Srivastava, A.K. Modulation of adenylate cyclase activity by Ca2+, phospholipid-dependent protein kinase in rat brain striatum. Mol Cell Biochem 92, 91–98 (1990). https://doi.org/10.1007/BF00220724

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