Cloning, pharmacological characterization, and polymorphism screening of the guinea pig β2-adrenoceptor

Jaap Oostendorp, Herman Meurs, S. Adriaan Nelemans, Johan Zaagsma, Henk F. Kauffman, Dirkje S. Postma, Hendrikus W.G.M. Boddeke, Knut Biber

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)

Abstract

In asthma, beta(2)-adrenoceptor agonist responsiveness has been associated with Arg16Gly and Gln27Glu polymorphisms of the beta(2)-adrenoceptor. Since the guinea pig is extensively used as an animal model for asthma, we investigated the occurrence of possible polymorphism of the guinea pig beta(2)-adrenoceptor. The guinea pig beta(2)-adrenoceptor coding region was amplified by sequence homology-based cloning. Homology of the translated protein with the human beta(2)-adrenoceptor was 88% with Ala at position 16 and Glu at position 27. Radioligand binding and cAMP-accumulation experiments of Chinese hamster ovary (CHO) cells transfected with the guinea pig beta(2)-adrenoceptor revealed a homogeneous population of functional receptors. Five degenerate single nucleotide polymorphisms were found within the beta(2)-adrenoceptor coding region of outbred Dunkin Hartley guinea pigs, at residues 354, 453, 483, 534 and 642. In conclusion, we have cloned the guinea pig beta(2)-adrenoceptor, which shows to be functional upon expression in a recombinant system and contains five single nucleotide polymorphisms dissimilar to human polymorphisms. (C) 2002 Elsevier Science B.V All rights reserved.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalEuropean Journal of Pharmacology
Volume457
Issue number1
DOIs
Publication statusPublished - 13-Dec-2002

Keywords

  • (Guinea pig)
  • beta(2)-adrenoceptor
  • molecular cloning
  • radioligand binding
  • cAMP
  • single nucleotide polymorphism
  • BETA-ADRENERGIC-RECEPTOR
  • AIRWAY SMOOTH-MUSCLE
  • DEPENDENT PROTEIN-KINASE
  • GENETIC POLYMORPHISMS
  • BETA-2-ADRENERGIC RECEPTOR
  • BRONCHIAL HYPERRESPONSIVENESS
  • SIGNAL-TRANSDUCTION
  • ASTHMATIC SUBJECTS
  • IN-VITRO
  • DESENSITIZATION

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