Oostendorp Jaap, Meurs Herman, Adriaan Nelemans S, Zaagsma Johan, Kauffman Henk F, Postma Dirkje S, Boddeke Hendrikus W G M, Biber Knut
Department of Molecular Pharmacology, University Centre for Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Eur J Pharmacol. 2002 Dec 13;457(1):1-10. doi: 10.1016/s0014-2999(02)02692-4.
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.
