α1-Adrenergic Receptors of MDCK-D1 Cells Utilize Multiple Signalling Components

  • Paul A. Insel
  • Rennolds S. Ostrom
  • Martin C. Michel
  • Rainer Büscher
Part of the Advances in Behavioral Biology book series (ABBI, volume 53)

Abstract

We have examined mechanisms for signal transduction by α1-adrenergic receptors in a clonal cell line, Madin Darby canine kidney, MDCK-D1 These cells possess a pure population of α1B-adrenergic receptors (α1B-AR) that activate multiple phospholipases. We show here that these receptors have 2 other actions: release of cellular ATP and increase in cyclic AMP formation. The increase in cyclic AMP formation depends on formation of cyclo-oxygenase-dependent products, in particular, PGE2. We also show here that P2Y receptor agonists down-regulate α1-AR in a non-additive manner with AR agonist-promoted down-regulation. Taken together, the data indicate that α1B-AR in MDCK-D1 cells use multiple mechanisms for activation and deactivation of signalling. Cellular release of and response to ATP may modulate α1B-AR signalling.

Keywords

Clonal Cell Line Cellular Release Stimulate cAMP Formation Multiple Signalling Component Multiple Phospholipase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Graham RM, Perez DM, Hwa J, and Piascik MT, α1-adrenergic receptor subtypes. Molecular structure, function, and signaling, Circ Res 78, 737–749 (1996).PubMedCrossRefGoogle Scholar
  2. 2.
    Zhong H, and Minneman KP, Alpha1-adrenoceptor subtypes, Eur J Pharmacol 375, 261–276 (1999).PubMedCrossRefGoogle Scholar
  3. 3.
    Insel PA, Balboa MA, Mochizuki N, Post SR, Urasawa K, and Xing M, Mechanisms for activation of multiple effectors by alpha 1-adrenergic receptors, Adv Pharmacol 42, 451–453 (1998).PubMedCrossRefGoogle Scholar
  4. 4.
    García-Sáinz JA, Vazquez-Prado J, and del Carmen Medina L, α1-adrenoceptors: function and phosphorylation, Eur J Pharmacol 389, 1–12 (2000).PubMedCrossRefGoogle Scholar
  5. 5.
    Balboa MA, and Insel PA, Stimulation of phospholipase D via α1-adrenergic receptors in Madin-Darby canine kidney cells is independent of PKCalpha and -epsilon activation, Mol Pharmacol 53, 221–227 (1998).PubMedGoogle Scholar
  6. 6.
    Yang M, Büscher R, Taguchi K, Greubbel B, Insel PA, and Michel MC, Protein kinase C does not mediate phenylephrine-induced down-regulation of Madin-Darby canine kidney cell alpha-1B adrenoceptors, J Pharmacol Exp Ther 286, 36–43 (1998).PubMedGoogle Scholar
  7. 7.
    Ostrom RS, Gregorian C, and Insel PA, Cellular release of and response to ATP as key determinants of the set-point of signal transduction pathways, J Biol Chem 275, 11735–11739 (2000).PubMedCrossRefGoogle Scholar
  8. 8.
    Meier KE, Sperling DM, and Insel PA, Agonist-mediated regulation of α1 and β2-adrenergic receptors in cloned MDCK cells, Am J Physiol 249, C69–77 (1985).Google Scholar
  9. 9.
    Schwiebert EM, ABC transporter-facilitated ATP conductive transport, Am J Physiol 276, C1–8 (1999).Google Scholar
  10. 10.
    Insel PA, Ostrom RS, Zambon AC, Hughes RJ, Balboa MA, Shehnaz D, Gregorian C, Torres B, Firestein BL, Xing M, and Post SR, P2Y receptors of MDCK cells: epithelial cell regulation by extracellular nucleotides, Clin Exp Pharmacol Physiol 28, 351–354 (2001).PubMedCrossRefGoogle Scholar
  11. 11.
    Lin RZ, Chen J, Hu ZW, and Hoffman BB, Phosphorylation of the cAMP response element-binding protein and activation of transcription by α1-adrenergic receptors, J Biol Chem 273, 30033–30038 (1998).PubMedCrossRefGoogle Scholar
  12. 12.
    Ruan Y, Kan H, Parmentier JH, Fatima S, Allen LF, and Malik KU, α1A-adrenergic receptor stimulation with phenylephrine promotes arachidonic acid release by activation of phospholipase D in rat-1 fibroblasts: inhibition by protein kinase A, J Pharmacol Exp Ther 284, 576–585 (1998).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Paul A. Insel
    • 1
  • Rennolds S. Ostrom
    • 1
  • Martin C. Michel
    • 2
  • Rainer Büscher
    • 1
    • 2
  1. 1.Department of PharmacologyUniversity of California, San DiegoLa JollaUSA
  2. 2.Departments of Medicine and PediatricsUniversity of EssenGermany

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