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Genomic cloning and species-specific properties of the recombinant canine beta(3)-adrenoceptor

Academic Article
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Overview

authors

  • Lenzen, G.
  • Pietri-Rouxel, F.
  • Drumare, M. F.
  • Amiard, A.
  • Guillot, S.
  • Archimbault, P.
  • Strosberg, Donny

publication date

  • December 1998

journal

  • European Journal of Pharmacology  Journal

abstract

  • A molecular clone encoding a beta3-adrenoceptor was isolated from a canine genomic library. The cloned receptor exhibited a pharmacological profile similar to that of other species: in particular, high efficiency of the two selective beta3-adrenoceptor agonists, CL 316,243 (disodium(R,R)-5[2[[2-(chlorophenyl)-2hydroxyethyl]-amino]propyl]- 1,3-benzodioxole-2,2-dicarboxylate) and ICI 201651 ((R)4-(2-hydroxy-3-phenoxypropylaminoethoxy)-N-(2-methoxyethyl)phe noxy acetic acid) and a low affinity for the radioligand (-)-[3-(125)I]-iodocyanopindolol. Interestingly, CGP 12177A ((+/-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one), which is described as a partial agonist for the human receptor, was a full agonist for the canine receptor. After expression and stimulation of the canine beta3-adrenoceptor in stably transfected Chinese hamster ovary cells there was a very low accumulation of cAMP, suggesting weak coupling to Gs-protein and adenylyl cyclase. However, the response was much better in human embryonal kidney cells transfected with the canine beta3-adrenoceptor gene. The cloning of the canine beta3-adrenoceptor and the insights gained from its pharmacological characterization may allow the development of selective compounds for use in the treatment of obese dogs.

subject areas

  • Adenylyl Cyclases
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Southern
  • CHO Cells
  • Cattle
  • Cells, Cultured
  • Cloning, Molecular
  • Cricetinae
  • DNA
  • Dogs
  • GTP-Binding Proteins
  • Humans
  • Molecular Sequence Data
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, beta-3
  • Recombinant Proteins
  • Sequence Alignment
  • Species Specificity
  • Transfection
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Research

keywords

  • (canine)
  • beta(3)-adrenoreceptor
  • molecular cloning
  • pharmacology
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Identity

International Standard Serial Number (ISSN)

  • 0014-2999

Digital Object Identifier (DOI)

  • 10.1016/s0014-2999(98)00809-7

PubMed ID

  • 9881593
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Additional Document Info

start page

  • 217

end page

  • 227

volume

  • 363

issue

  • 2-3

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