Identification and Characterization of Non-Adrenergic Binding Sites in Insulin-Secreting Cells with the Imidazoline RX821002

  • Susan L. F. Chan
  • Kay E. Scarpello
  • Noel G. Morgan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 426)


Recent studies have shown that certain compounds which possess an imidazoline moiety within their structure, are able to enhance the rate of insulin secretion, both in vivo and in vitro 1. 86Rb+ efflux experiments and electrophysiological studies2,3 have provided evidence that this response is due to the reduction in potassium flux via ATP-regulated K+ channels across the islet B-cell plasma membrane, resulting in membrane depolarization. The nature of the binding site mediating the effects of imidazolines in islets is unclear but it is significant that a class of binding sites known as “imidazoline-preferring” receptors has recently been described in a wide variety of tissues4. However, the pharmacology of the defined I1- and I2-imidazoline sites does not correlate with the observed responses to imidazolines in islets, although I2-receptors (also known as non-adrenoceptor idazoxan binding sites (NAIBS)) have been described in pancreatic islets5 and RINm5F insulinoma cells6. Moreover, we have shown that the secretory response induced by the imidazoline efaroxan shows stereoselectivity and is subject to down-regulation in the presence of agonist7. Thus, the possibilty remains the islet imidazoline receptor may represent a novel, third type of imidazoline binding site.


Insulin Secretion Insulin Release Radioligand Binding Experiment Imidazoline Compound Secretagogue Activity 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    S.L.F. Chan, Role of α2-adrenoceptors and imidazoline-binding sites in the control of insulin secretion, Clin. Sci. 85: 671 (1993).PubMedGoogle Scholar
  2. 2.
    S.L.F. Chan, M.J. Dunne, M.R. Stillings, and N.G. Morgan, The α2-adrenoceptor antagonist efaroxan modulates K+ ATP channels in insulin-secreting cells, Eur. J. Pharmacol. 204: 41 (1991).PubMedCrossRefGoogle Scholar
  3. 3.
    J.-C. Jonas, T.D. Plant, and J.C. Henquin, Imidazoline antagonists of α2-adrenoceptors increase insulin release in vitro by inhibiting ATP-sensitive K+ channels in pancreatic β-cells, Br. J. Pharmacol. 107: 8 (1992).PubMedCrossRefGoogle Scholar
  4. 4.
    M.C. Michel, and P. Ernsberger, Keeping an eye on the I site: imidazoline-preferring receptors, Trends Pharmacol. Sci. 45: 369 (1992).Google Scholar
  5. 5.
    C.A. Brown, A.C. Loweth, S.A. Smith, and N.G. Morgan, Stimulation of insulin secretion by imidazoline compounds is not due to interaction with non-adrenoceptor idazoxan binding sites, Br. J. Pharmacol. 108: 312 (1993).PubMedCrossRefGoogle Scholar
  6. 6.
    A. Remaury, and H. Paris, The insulin-secreting cell line, RINm5F, expresses an alpha-2D adrenoceptor and nonadrenergic idazoxan-binding sites, J. Pharmacol. Exp. Ther. 260: 417 (1992).PubMedGoogle Scholar
  7. 7.
    S.L.F. Chan, C.A. Brown, and N.G. Morgan, Stimulation of insulin secretion by the imidazoline α2-adrenoceptor antagonist efaroxan is mediated by a novel, stereoselective, binding site, Eur: J. Pharmacol. 230: 375 (1993).CrossRefGoogle Scholar
  8. 8.
    D. Langin, M. Lafontan, M.R. Stillings, and H. Paris, [3H]-RX821002: A new tool for the identification of a2A-adrenoceptors, Em: J. Pharmacol. 167: 95 (1989).CrossRefGoogle Scholar
  9. 9.
    W. Montague, and K.W. Taylor, Pentitols and insulin release by isolated rat islets of Langerhans, Biochem. J. 109: 339 (1968).Google Scholar
  10. 10.
    G.O. Gey, and M.K. Gey, Maintenance of human normal cells in continuous culture: preliminary report; cultivation of mesoblastic tumors and normal cells and notes on methods of cultivation, Am. J. Cancer 27: 45 (1936).CrossRefGoogle Scholar
  11. 11.
    P.K. Smith, R.I. Krohn, G.T. Hermanson, A.K. Mallia, F.H. Gartner, M.D. Provenzano, E.K. Fujimoto, N.M. Goeke, B.J. Olson, and D.C. Klenk, Measurement of protein using bicinchoninic acid, Anal. Biochem. 150: 76 (1985).PubMedCrossRefGoogle Scholar
  12. 12.
    S.L.F Chan, M.R. Stillings, and N.G. Morgan, Mechanisms involved in stimulation of insulin secretion by the hypoglycaemic alpha-adrenergic antagonist, DG-5128, Biochem. Biophys. Res. Commun. 176: 1545 (1991).PubMedCrossRefGoogle Scholar
  13. 13.
    A. Schulz, and A. Hassleblatt, Dual action of clonidine on insulin release: suppression but stimulation when α2-adrenoceptors are blocked, Naunyn-Schmiedeberg’s Arch. Pharmacol. 340: 305 (1989).Google Scholar
  14. 14.
    P.R. Ernsberger, K.L Westbrook, O. Christen, and S.G. Schäfer, A second generation of centrally acting antihypertensive agents act on putative I1-imidazoline receptors, J. Cardiovasc. Pharmacol. 20: S1 (1992).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Susan L. F. Chan
    • 1
  • Kay E. Scarpello
    • 1
  • Noel G. Morgan
    • 1
  1. 1.Cellular Pharmacology Group, Department of Biological SciencesKeele UniversityKeele, StaffsUK

Personalised recommendations