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Alterations in G-Protein-Linked Signal Transduction in Vascular Smooth Muscle in Diabetes

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Diabetes and Cardiovascular Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 498))

Abstract

The present studies were undertaken to determine the levels of stimulatory and inhibitory guanine nucleotide regulatory proteins (Gs and Gi respectively) and their relationship with adenylyl cyclase activity in aorta from 5-day streptozotocin-induced diabetic (STZ) rats. The levels of Giα-2 as determined by immunoblotting techniques using AS/7 antibody were significantly decreased by about 60% in STZ as compared to control rats, whereas the levels of Gsa were not altered. In addition, the stimulatory effect of cholera toxin (CT) on GTP-sensitive adenylyl cyclase was not different in STZ as compared to control rats. On the other hand, the stimulatory effects of GTPγS, isoproterenol, glucagon, forskolin (FSK) and sodium fluoride on adenylyl cyclase were enhanced in STZrats. Furthermore, GTPγS inhibited FSK-stimulated adenylyl cyclase activity in a concentration-dependent manner (receptor independent functions of Gi) in control rats which was almost completely abolished in STZ rats. In addition, receptor-mediated inhibition of adenylyl cyclase by angiotensin II (AII), oxotremorine and atrial natriuretic peptide (ANP) was attenuated in STZ rats. These results suggest that the decreased expression of Giα, but not of Gsα, may be responsible for the observed altered responsiveness of adenylyl cyclase to hormonal stimulation and inhibition in STZ-rats. It may thus be suggested that the decreased Gi activity may be one of the possible mechanisms responsible for the impaired vascular functions in diabetes.

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References

  1. Neer EJ. Heterotrimeric G proteins. Organizers of transmembrane signals. Cell 1995; 80:249–257.

    Article  PubMed  CAS  Google Scholar 

  2. Fleming JW, Wisler PL, Watanabe AM. Signal transduction by G-proteins in cardiac tissues. Circulation 1992;85:420–433.

    Article  PubMed  CAS  Google Scholar 

  3. Murakami T, Yasuda H. Rat heart cell membranes contain three substrate for cholera toxin-catalyzed ADP-ribosylation and a single substrate for Pertussis toxin-catalyzed ADP-ribosylation. Biochem. Biophys. Res. Commun. 1986;138:1355–1361.

    Article  PubMed  CAS  Google Scholar 

  4. Robishaw JD, Smigel MD, Gilman AG. Molecular basis for two forms of the G-protein that stimulate adenylate cyclase. J. Biol. Chem. 1986;261:9587–9590.

    PubMed  CAS  Google Scholar 

  5. Bray P, Caster A, Simons C, Guo V, Puckett C, Hamholz J, Spiegel A, Nirenberg H. Human cDNA clones for four species of Gsa signal transduction protein. Proc. Natl. Acad. Sci. U.S.A. 1986;83:8893–8897.

    Article  PubMed  CAS  Google Scholar 

  6. Itoh H, Kozaka T, Magata S, Nakamura S, Katada T, Ui M, Iwai S, Ohtsuka E, Kawasaki H, Suzuki K, Kaziro Y. Molecular cloning and sequence determination of cDNAs for a subunits of the guanine nucleotide-binding proteins Gs, Gi and Go from brain. Proc. Natl. Acad. Sci. U.S.A. 1986;83:3776–3780.

    Article  PubMed  CAS  Google Scholar 

  7. Itoh H, Toyama R, Kozasa T, Tsukamoto T, Matsuoka M, Kaziro Y. Presence of three distinct molecular species of Gi protein: a subunit structure of rat cDNA and human genomic DNAs. J. Biol. Chem. 1988;263:6656–6664.

    PubMed  CAS  Google Scholar 

  8. Wong YH, Conklin BB, Boume HR. G2-mediated hormonal inhibition of cyclic AMP accunulation. Science 1992;255:339–342.

    Article  PubMed  CAS  Google Scholar 

  9. Yatani A, Mattera R, Codina J. The G-protein gated atrial K’ channels is stimulated by three distinct Gia subunits. Nature 1988;336:680–682.

    Article  PubMed  CAS  Google Scholar 

  10. Simon MI, Strathmann MP, Gautam N.XXX Science 1991;252:802–808.

    Article  PubMed  CAS  Google Scholar 

  11. Cali JJ, Balcueva EA, Rybalkin I, Robishaw JD. Selective tissue distribution of G protein y subunits, including a new form of the y subunits identified by cDNA cloning. J. Biol. Chem. 1992;267:24023–24027.

    PubMed  CAS  Google Scholar 

  12. Tang W-J, Gilman AG. Type-specific regulation of adenylyl cyclase by G protein (3y subunits. Science 1991; 254:1500–1503.

    Article  PubMed  CAS  Google Scholar 

  13. Wickman KD, Iniguez-Liuhi JA, Davenport PA, Taussig R, Krapivinski GB, Linder ME, Gilman AG, Clapham DE. Recombinant G-protein 3y subunit activate the muscarinic-gated atrial potassium channel. Nature 1994;368:255–257.

    Article  PubMed  CAS  Google Scholar 

  14. Tang W-J, Gilman AG. Adenylyl cyclase. Cell 1992;70:869–872.

    Article  PubMed  CAS  Google Scholar 

  15. Premont RT, Chen J, Ma H-W, Ponnapalli M, Iyengar R. Two members of a widely expressed subfamily of hormone-stimulated adenylyl cyclases. Proc. Natl. Acad. Sci U.S.A 1992;89:98099813.

    Google Scholar 

  16. Katsushika S, Chen L, Kawabe J-I, Nilakantan R, Halnon NJ, Homcy CJ, Ishikawa Y. Cloning andcharacterization of a sixth adenylyl cyclase isoform: type V and VI constitute a subgroup withinthe mammalian adenylyl cyclase family. Proc. Natl. Acad. Sci. U.S.A 1992;89:8774–8778.

    Article  PubMed  CAS  Google Scholar 

  17. Katz AM, Tada M, Kirchberger MA. Control of calcium transport in the myocardium by the cyclic AMP-protein kinase system. Adv. Cyclic Nucleotide Res. 1975;5:453–472.

    PubMed  CAS  Google Scholar 

  18. Keely SL Jr, Lincoln TM, Corbin JD. Interaction of acetylcholine and epinephrine on heart cyclic AMP-dependent protein kinase. Am. J Physiol. 1978;234:H432–H438.

    PubMed  CAS  Google Scholar 

  19. Triner L, Vulliemoz Y, Verosky M, Habif DV, Nahas VV. Adenylyl cyclase phosphodiesterase system in arterial smooth muscle. Life Sci 1972; 11:817–824.

    Article  CAS  Google Scholar 

  20. Bar H-P. Cyclic nucleotides and smooth muscle. Adv. Cyclic nucleotide Res. 1974;4:195–237.

    Google Scholar 

  21. Feldman AM, Cates AE, Veazey WB, Hershberger RE, Bristow MR, Baughman KL, Baumgartner WA, Dop CV. Increase of the 40,000 mol wt pertussis toxin substrate (G-protein) in the failing human heart..1 Clin Invest 1988;82:189–197.

    Article  CAS  Google Scholar 

  22. Malbon CC, Rapiejko PJ, Watkins DC. Permissive hormone regulation of hormone-sensitive effector systmes. Trends Pharmacol Sci 1988;9:33–36.

    Article  PubMed  CAS  Google Scholar 

  23. Anand-Srivastava MB. Enhanced expression of inhibitory guanine nucleotide regulatory protein in spontaneously hypertensive rats: relationship to adenylate cyclase inhibition. Biochem J 1992;288:79–85.

    PubMed  CAS  Google Scholar 

  24. Thibault C, Anand-Srivastava MB. Altered expression of G-protein mRNA in spontaneously hypertensive rats. FEBS Lett 1992;313:160–164.

    Article  PubMed  CAS  Google Scholar 

  25. Anand-Srivastava MB, de Champlain, Thibault C. DOCA-salt hypertensive rat hearts exhibit altered expression of G-protiens. Am JHypertens 1993;6:72–75.

    CAS  Google Scholar 

  26. Lynch CJ, Blackmore PF, Johnson EH,Wange RL, Krone, PK, Exton JH. Guanine nucleotide binding regulatory proteins and adenylate cyclase in livers of streptozotocin-and BB/Wor-diabtic rats. Immunodetection of Gs and Gi with antisera prepared against synthetic peptides. J Clin Invest 83:2050–2062.

    Google Scholar 

  27. Bushfield M, Griffiths SL, Strassheim D, Tang E, Shakur Y, Lavan B, Houslay MD. Guaninenucleotide-binding proteins in diabetes and insulin-resistant states. Biochem Soc Symp 1990; 56:137–154.

    PubMed  CAS  Google Scholar 

  28. Gawler D, Milligan G, Spiegel AM, Unson CG, Houslay MD. Aboltion of the expression f inhibitory guanine nucleotide regulatory protein Gi activity in diabetes. Nature 1987;327:229–232.

    Article  PubMed  CAS  Google Scholar 

  29. Bushfield M, Griffiths SL, Murphy GJ, Pyne, NJ, Knowler JT, Milligan G, Parker PJ, Mollnr S, Houslay MD. Diabetes-induced alterations in the expressio, functioning and phosphorylation state of the inhibitory guanine nucleotide regulatory protein Gi-2 in hepatocytes. Biochem J 1990;271:365–372.

    PubMed  CAS  Google Scholar 

  30. Salomon Y, Londos C, Rodbell M. A highly sensitive adenylate cyclase assay. Anal Biochem 1974;58:541–548.

    Article  PubMed  CAS  Google Scholar 

  31. Lowry OM, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. JBiol Chem 1951;193:265–275.

    CAS  Google Scholar 

  32. Jones DT, Reed RR. Molecular cloning of five GTP-binding protein cDNA species from rat olfactory neuroepithelium. JBiol Chem 1987; 262:14241–14249.

    CAS  Google Scholar 

  33. Anand-Srivatava MB, Srivastava AK, Cantin M. Pertussis toxin attenuates atrial natriuretic factor-mediated inhibtion of adenylate cyclase. Involvement of inhibitory guanine nucleotide regulatory protein. JBiol Chem 1987;262:4931–4934.

    Google Scholar 

  34. Anand-Srivastava MB, Sairam MR, Cantin M. Ring-deleted analogs of atrial natriuretic factor inhibits adenylyl cyclase/cAMP system: possible coupling of clearance atrial natriuretic factor receptors to adenylate cyclase/cAMP signal transduction system. J Biol Chem 1990;265:8566–8572

    PubMed  CAS  Google Scholar 

  35. Anand-Srivastava MB. Angiotensin II receptors negatively coupled to adenylate cyclase in rat myocardial sarcolemma: involvement of inhibitory guanine nucleotide protein. Bniochem Pharmacol 1989;38:489–496.

    Article  CAS  Google Scholar 

  36. Swithers SE, Stewart RE, McCarty R. Binding sites for atrial natriuretic factor (ANF) in kidneys and adrenal glands of spontaneously hypertensive (SHR) rats. Life Sci 1987;1673–1681.

    Google Scholar 

  37. Schiffrin EL. Decreased density of binding sites for atrial natriuretic peptide on platelets of patients with severe congestive heart failure. Clin Sci 1988;74:213–218.

    Google Scholar 

  38. Limas C, Limas CJ. Reduced number of ß-adrenergic recpetors in the myocardium of spontaneously hypertensive rats. Biochem Biophys Res Commun 1978;83:710–714.

    Article  PubMed  CAS  Google Scholar 

  39. Anand-Srivastava MB. Amiloride interacts with guanine nucletoide regulatory proteins and attenuates the hormonal inhibition of adenylate cyclase. JBiol Chem 1989;264:9491–9496.

    CAS  Google Scholar 

  40. Hildebrandt JD, Hanoune J, Birnbaumer J. Guanine nucleotide inhibition of cyc-S49 mouse lymphoma cell membrane adenylyl cyclase. JBiol them 1982;257:14723–14725.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada

    Madhu B. Anand-Srivastava, Rui Wang & Yi Yong Liu

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  1. Madhu B. Anand-Srivastava
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  2. Rui Wang
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  3. Yi Yong Liu
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Editor information

Editors and Affiliations

  1. Diabetes Research and Treatment Centre, Winnipeg, Canada

    Aubie Angel

  2. St. Boniface Research Centre, Winnipeg, Canada

    Naranjan Dhalla , Grant Pierce  & Pawan Singal ,  & 

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© 2001 Springer Science+Business Media New York

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Anand-Srivastava, M.B., Wang, R., Liu, Y.Y. (2001). Alterations in G-Protein-Linked Signal Transduction in Vascular Smooth Muscle in Diabetes. In: Angel, A., Dhalla, N., Pierce, G., Singal, P. (eds) Diabetes and Cardiovascular Disease. Advances in Experimental Medicine and Biology, vol 498. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1321-6_33

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  • DOI: https://doi.org/10.1007/978-1-4615-1321-6_33

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5496-3

  • Online ISBN: 978-1-4615-1321-6

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