β1-adrenoceptors compensate for β3-adrenoceptors in ileum from β3-adrenoceptor knock-out mice

I This study examines beta (1)-, beta (2)- and beta (3)-adrenoceptor (AR)-mediated responses. mRNA levels and radioligand binding in ileum from beta (3)-AR knock-out(-/-) (KO) and wild type(+/+) (FVB) mice. 2 In KO and FVB mice, SR59230A (100 nM) (beta (3)-AR antagonist) antagonized responses to (-)- isoprenaline in both KO and FVB mice. (-)-Isoprenaline mediated relaxation of ileum was antagonized weakly by ICI118551 (100 nM) (beta (2)-AR antagonist). Responses to (-)-isoprenaline were more strongly antagonized by CGP20712A (100 nM) (beta (1)-AR antagonist), propranolol (1 muM) (beta (1)-/beta (2)-AR antagonist), carvedilol (100 nM) (non-specific P-AR antagonist), and CGP12177A (100 nM) (beta (1)-/beta (2)-AR antagonist) in ileum from KO than in FVB mice. 3 Responses to CL316243 (B-AR agonist) in ileum from FVB mice were antagonized by SR59230A (100 nM) but not by propranolol (1 muM) or carvedilol (100 nM). CL316243 was ineffective in relaxing ileum from KO mice. 4 CGP12177A had no agonist actions in ileum from either KO or FVB mice. 5 PI-AR mRNA levels were increased 3 fold in ileum from KO compared to FVB mice. This was associated with an increased maximum number of beta (1)-/beta (2)-AR binding sites (B-max). beta (2)-AR mRNA levels were unaffected while no beta (3)-AR mRNA was detected in KO mice. 6 In mouse ileum, beta (3)-ARs and to a lesser extent beta (1)-ARs are the predominant adrenoceptor subtypes mediating relaxation in ileum from FVB mice. In KO mice beta (1)-ARs functionally compensate for the lack of beta (3)-ARs, and this is associated with increased beta (1)-AR mRNA and levels of binding.