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Involvement of calmodulin in realization of vasoconstrictive effects of serotonin and norepinephrine

  • Animal and Human Physiology
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Abstract

The involvement of calmodulin in adrenergic and serotoninergic regulation of vascular contractility has been studied. Calmodulin inhibitors trifluoperazine and W-13 suppress vasoconstriction of the rat aorta in response to norepinephrine, serotonin, and serotonin 5HT1A and 5HT2A receptor agonists (8-OH-DPAT and DOI, respectively) and do not affect the vasodilatory effect of 5HT1B, 5HT2B, and 5HT4 receptors. The force of aorta contraction in response to 8-OH-DPAT increases after the activation of calcium entry through voltage-gated Ca2+ channels. This effect is not related to nonspecific activation of α1-adrenoceptors, since it is realized in the presence of prazosin. The inhibitor of calmodulin-dependent myosin light chain kinase KN93 decreases the vasoconstrictive response to norepinephrine and serotonin by only 20%. Calmodulin inhibitors slightly decrease aortic constriction in response to endothelin-1, vasopressin, angiotensin II, and KCl. Trifluoperazine does not suppress vasoconstriction induced by the G protein activator AlF 4 . It is assumed that the target of trifluoperazine and W-13 is calmodulin interacting directly with α1-adrenoceptors and serotonin (5HT1A and 5HT2A) receptors.

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References

  • Avdonin, P.V. and Kozhevnikova, L.M., Regulation of Expression and Functional Activity of G Protein-Coupled Receptors. Disturbance of These Processes in Pathologies, Biol. Membr., 2007, vol. 24, no. 1, pp. 4–31.

    CAS  Google Scholar 

  • Bal, M., Zaika, O., Martin, P., and Shapiro, M.S., Calmodulin Binding to M-Type K-Channels Assayed by TIRF/FRET in Living Cells, J. Physiol., 2008, vol. 586, pp. 2307–2320.

    Article  PubMed  CAS  Google Scholar 

  • Bal, M., Zhang, J., Hernandez, C.C., et al., Ca2+/Calmodulin Disrupts AKAP79/150 Interactions with KCNQ (M-Type) K+ Channels, J. Neurosci., 2010, vol. 30, no. 6, pp. 2311–2323.

    Article  PubMed  CAS  Google Scholar 

  • Belcheva, M.M., Szùcs, M., Wang, D., et al., mu-Opioid Receptor-Mediated ERK Activation Involves Calmodulin-Dependent Epidermal Growth Factor Receptor Transactivation, J. Biol. Chem., 2001, vol. 276, no. 36, pp. 33847–33853.

    Article  PubMed  CAS  Google Scholar 

  • Bofill-Cardona, E., Kudlacek, O., Yang, Q., et al., Binding of Calmodulin to the D2-Dopamine Receptor Reduces Receptor Signaling by Arresting the G Protein Activation Switch, J. Biol. Chem., 2000, vol. 275, no. 42, pp. 32672–32680.

    Article  PubMed  CAS  Google Scholar 

  • Castillo, C., Ibarra, M., Marquez, J.A., et al., Pharmacological Evidence for Interactions between 5-HT1A Receptor Agonists and Subtypes of Alpha 1-Adrenoceptors on Rabbit Aorta, Eur. J. Pharmacol., 1993, vol. 241, nos. 2–3, pp. 141–148.

    Article  PubMed  CAS  Google Scholar 

  • Ferr, S., Woods, A.S., Navarro, G., et al., Calcium-Mediated Modulation of the Quaternary Structure and Function of Adenosine A2A-Dopamine D2 Receptor Heteromers, Curr. Opin. Pharmacol., 2010, vol. 10, no. 1, pp. 67–72.

    Article  Google Scholar 

  • Gardiner, E.E., Arthur, J.F., Berndt, M.C., and Andrews, R.K., Role of Calmodulin in Platelet Receptor Function, Curr. Med. Chem. Cardiovasc. Hematol. Agents, 2005, vol. 3, no. 4, pp. 283–287.

    Article  PubMed  CAS  Google Scholar 

  • Kozhevnikova, L.M., Davydova, A.G., and Avdonin, P.V., Plasma Membrane Depolarization and Activation of Receptors for Endogenous Vasoconstrictors as Possible Mechanisms of Potentiation of Vasoconstrictive Response to Serotonin in Traumatic Shock in Rats, Biol. Bull., 2009, vol. 36, no. 3, pp. 285–297.

    Article  CAS  Google Scholar 

  • Kozhevnikova, L.M. and Avdonin, P.V., Agonist of Serotonin 5HT1A-Receptors 8-OH-DPAT Increases the Force of Contraction of Rat Aorta and Mesenteric Artery in the Presence of Endothelin-1 or Vasopressin and Causes Relaxation of the Vessels Preconstricted with Noradrenaline, Biol. Bull., 2010, vol. 37, no. 1, pp. 35–43.

    Article  CAS  Google Scholar 

  • Kozhevnikova, L.M., Sukhanova, I.F., and Avdonin, P.V., Activation of “Silent” Vasoconstrictive 5-HT1A Receptors as a Possible Mechanism of Synergism in Angiotensin II and Serotonin Effect on Vascular Tone, Biol. Bull., 2011, vol. 38, no. 1, pp. 57–64.

    Article  CAS  Google Scholar 

  • Labasque, M., Reiter, E., Becamel, C., et al., Physical Interaction of Calmodulin with the 5-Hydroxytryptamine 2C Receptor C-Terminus Is Essential for G Protein-Independent, Arrestin-Dependent Receptor Signaling, Mol. Biol. Cell, 2008, vol. 9, no. 11, pp. 4640–4650.

    Article  Google Scholar 

  • Matsushima, N., Hayashi, N., Jinbo, Y., and Izumi, Y., Ca2+-Bound Calmodulin Forms a Compact Globular Structure on Binding Four Trifluoperazine Molecules in Solution, Biochem. J., 2000, vol. 347, pp. 211–215.

    Article  PubMed  CAS  Google Scholar 

  • Minakami, R., Jinnai, N., and Sugiyama, H., Phosphorylation and Calmodulin Binding of the Metabotropic Glutamate Receptor Subtype 5 (mGluR5) Are Antagonistic in vitro, J. Biol. Chem., 1997, vol. 272, no. 32, pp. 20291–20298.

    Article  PubMed  CAS  Google Scholar 

  • Nakajima, Y., Yamamoto, T., Nakayama, T., and Nakanishi, S., A Relationship between Protein Kinase C Phosphorylation and Calmodulin Binding to the Metabotropic Glutamate Receptor Subtype 7, J. Biol. Chem., 1999, vol. 274, no. 39, pp. 27573–27577.

    Article  PubMed  CAS  Google Scholar 

  • Nakayama, H., Numakawa, T., Ikeuchi, T., and Hatanaka, H., Nicotine-Induced Phosphorylation of Extracellular Signal-Regulated Protein Kinase and CREB in PC12 Cells, J. Neurochem., 2001, vol. 79, pp. 489–498.

    Article  PubMed  CAS  Google Scholar 

  • Oláh, Z., Jósvay, K., Pecze, L., et al., Anti-Calmodulins and Tricyclic Adjuvants in Pain Therapy Block the TRPV1 Channel, PLoS One, 2007, vol. 2, no. 6, p. e545.

    Article  PubMed  Google Scholar 

  • Quinn, J.C., Johnson-Farley, N.N., Yoon, J., and Cowen, D.S., Activation of Extracellular-Regulated Kinase by 5-Hydroxytryptamine(2A) Receptors in PC12 Cells Is Protein Kinase C-Independent and Requires Calmodulin and Tyrosine Kinases, J. Pharmacol. Exp. Ther., 2002, vol. 303, no. 2, pp. 746–752.

    Article  PubMed  CAS  Google Scholar 

  • Raymond, J.R., Turner, J.H., Gelasco, A.K., et al., 5-HT Receptor Signal Transduction Pathways, in The Receptors: The Serotonin Receptors: From Molecular Pharmacology to Human Therapeutics, Roth, B.L., Ed., Totowa, New Jersey: Humana Press, 2006, pp. 143–207.

    Google Scholar 

  • Rellos, P., Pike, A.C., Niesen, F.H., et al., Structure of the CaMKIIdelta/Calmodulin Complex Reveals the Molecular Mechanism of CaMKII Kinase Activation, PLoS Biol., 2010, vol. 8, no. 7, p. e1000426.

    Article  PubMed  Google Scholar 

  • Ritter, S.L. and Hall, R.A., Fine-Tuning of GPCR Activity by Receptor-Interacting Proteins, Nat. Rev. Mol. Cell Biol., 2009, vol. 10, no. 12, pp. 819–830.

    Article  PubMed  CAS  Google Scholar 

  • Rossi, N.F. and Schrier, R.W., Anti-Calmodulin Agents Affect Osmotic and Angiotensin II-Induced Vasopressin Release, Am. J. Physiol., 1989, vol. 256, no. 4, pp. E516–E523.

    PubMed  CAS  Google Scholar 

  • Rossi, N.F., Effect of Anti-Calmodulin Agents on Vasopressin Release in vitro to Depolarization and Calcium Ionophore, Life Sci., 1990, vol. 46, no. 15, pp. 1091–1098.

    Article  PubMed  CAS  Google Scholar 

  • Sánchez-González, P., Jellali, K., and Villalobo, A., Calmodulin-Mediated Regulation of the Epidermal Growth Factor Receptor, FEBS J., 2010, vol. 277, no. 2, pp. 327–342.

    Article  PubMed  Google Scholar 

  • Sengupta, P., Ruano, M.J., Tebar, F., et al., Membrane-Permeable Calmodulin Inhibitors (e.g. W-7/W-13) Bind to Membranes, Changing the Electrostatic Surface Potential: Dual Effect of W-13 on Epidermal Growth Factor Receptor Activation, J. Biol. Chem., 2007, vol. 282, no. 11, pp. 8474–8486.

    Article  PubMed  CAS  Google Scholar 

  • Smith, J.R., Kim, C., Kim, H., et al., Precontraction with Elevated Concentrations of Extracellular Potassium Enables Both 5-HT1B and 5-HT2A “Silent” Receptors in Rabbitear Artery, J. Pharmacol. Exp. Ther., 1999, vol. 289, no. 1, pp. 354–360.

    PubMed  CAS  Google Scholar 

  • Tebar, F., Villalonga, P., Sorkina, T., et al., Calmodulin Regulates Intracellular Trafficking of Epidermal Growth Factor Receptor and the MAPK Signaling Pathway, Mol. Biol. Cell, 2002, vol. 13, pp. 2057–2068.

    Article  PubMed  CAS  Google Scholar 

  • Turner, J.H., Gelasco, A.K., and Raymond, J.R., Calmodulin Interacts with the Third Intracellular Loop of the Serotonin 5-Hydroxytryptamine1A Receptor at Two Distinct Sites: Putative Role in Receptor Phosphorylation by Protein Kinase C, J. Biol. Chem., 2004, vol. 279, no. 17, pp. 17027–17037.

    Article  PubMed  CAS  Google Scholar 

  • Turner, J.H. and Raymond, J.R., Interaction of Calmodulin with the Serotonin 5-Hydroxytryptamine2A Receptor. A Putative Regulator of G Protein Coupling and Receptor Phosphorylation by Protein Kinase C, J. Biol. Chem., 2005, vol. 280, no. 35, pp. 30741–30750.

    Article  PubMed  CAS  Google Scholar 

  • Vetter, W.S. and Leclerc, E., Novel Aspects of Calmodulin Target Recognition and Activation, Eur. J. Biochem. FEBS, 2003, vol. 270, pp. 404–414.

    Article  CAS  Google Scholar 

  • Villalobos-Molina, R., Orozco-Mendez, M., Lopez-Guerrero, J.J., et al., WAY 405, a New Silent 5-HT (1A) Receptor Antagonist with Low Affinity for Vascular Alpha (1)-Adrenoceptors, Auton. Autacoid. Pharmacol., 2005, vol. 25, no. 4, pp. 185–189.

    Article  PubMed  CAS  Google Scholar 

  • Villalon, C.M. and Centurion, D., Cardiovascular Responses Produced by 5-Hydroxytriptamine: A Pharmacological Update on the Receptors/Mechanisms Involved and Therapeutic Implications, Naunyn Schmiedebergs Arch. Pharmacol., 2007, vol. 376, nos. 1–2, pp. 45–63.

    Article  PubMed  CAS  Google Scholar 

  • Yoshio, R., Taniguchi, T., Itoh, H., et al., Affinity of Serotonin Receptor Antagonists and Agonists to Recombinant and Native Alpha1-Adrenoceptor Subtypes, Jpn. J. Pharmacol., 2001, vol. 86, no. 2, pp. 189–195.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, M. and Yuan, T., Molecular Mechanisms of Calmodulin’s Functional Versatility, Biochem. Cell Biol., 1998, vol. 76, nos. 2–3, pp. 313–323.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to L. M. Kozhevnikova.

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Original Russian Text © L.M. Kozhevnikova, P.V. Avdonin, 2012, published in Izvestiya Akademii Nauk, Seriya Biologicheskaya, 2012, No. 4, pp. 430–437.

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Kozhevnikova, L.M., Avdonin, P.V. Involvement of calmodulin in realization of vasoconstrictive effects of serotonin and norepinephrine. Biol Bull Russ Acad Sci 39, 360–367 (2012). https://doi.org/10.1134/S1062359012030065

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