Genomic cloning and species-specific properties of the recombinant canine beta3-adrenoceptor.
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.
Lenzen
G
G
Vetigen, Paris, France.
Pietri-Rouxel
F
F
Drumare
M F
MF
Amiard
A
A
Guillot
S
S
Archimbault
P
P
Strosberg
A D
AD
D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D016466:CHO Cells; D002417:Cattle; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006224:Cricetinae; D004247:DNA; D004285:Dogs; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011943:Receptors, Adrenergic, beta / Q000235:genetics* / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013045:Species Specificity; D014162:Transfection
D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D011994:Recombinant Proteins; D004247:DNA; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases