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Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry

Academic Article
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Overview

authors

  • Rohrer, S. P.
  • Birzin, E. T.
  • Mosley, R. T.
  • Berk, S. C.
  • Hutchins, S. M.
  • Shen, D. M.
  • Xiong, Y. S.
  • Hayes, E. C.
  • Parmar, R. M.
  • Foor, F.
  • Mitra, S. W.
  • Degrado, S. J.
  • Shu, M.
  • Klopp, J. M.
  • Cai, S. J.
  • Blake, A.
  • Chan, W. W. S.
  • Pasternak, A.
  • Yang, L. H.
  • Patchett, A. A.
  • Smith, Roy
  • Chapman, K. T.
  • Schaeffer, J. M.

publication date

  • 1998

journal

  • Science  Journal

abstract

  • Nonpeptide agonists of each of the five somatostatin receptors were identified in combinatorial libraries constructed on the basis of molecular modeling of known peptide agonists. In vitro experiments using these selective compounds demonstrated the role of the somatostatin subtype-2 receptor in inhibition of glucagon release from mouse pancreatic alpha cells and the somatostatin subtype-5 receptor as a mediator of insulin secretion from pancreatic beta cells. Both receptors regulated growth hormone release from the rat anterior pituitary gland. The availability of high-affinity, subtype-selective agonists for each of the somatostatin receptors provides a direct approach to defining their physiological functions.

subject areas

  • Amides
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cells, Cultured
  • Cricetinae
  • Drug Design
  • Glucagon
  • Growth Hormone
  • Insulin
  • Islets of Langerhans
  • Ligands
  • Membrane Proteins
  • Mice
  • Models, Chemical
  • Molecular Sequence Data
  • Pituitary Gland, Anterior
  • Rats
  • Receptors, Somatostatin
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Identity

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.282.5389.737

PubMed ID

  • 9784130
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Additional Document Info

start page

  • 737

end page

  • 740

volume

  • 282

issue

  • 5389

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