Abstract
In asthma, β 2-adrenoceptor agonist responsiveness has been associated with Arg16Gly and Gln27Glu polymorphisms of the β 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 β 2-adrenoceptor. The guinea pig β 2-adrenoceptor coding region was amplified by sequence homology-based cloning. Homology of the translated protein with the human β 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 β 2-adrenoceptor revealed a homogeneous population of functional receptors. Five degenerate single nucleotide polymorphisms were found within the β 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 β 2-adrenoceptor, which shows to be functional upon expression in a recombinant system and contains five single nucleotide polymorphisms dissimilar to human polymorphisms.
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