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

OnderzoeksoutputAcademicpeer review

7 Citaten (Scopus)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)1-10
Aantal pagina's10
TijdschriftEuropean Journal of Pharmacology
Volume457
Nummer van het tijdschrift1
DOI's
StatusPublished - 13-dec.-2002

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