β 1 ‐Adrenoceptors compensate for β 3 ‐adrenoceptors in ileum from β 3 ‐adrenoceptor knock‐out mice

This study examines β 1 ‐, β 2 ‐ and β 3 ‐adrenoceptor (AR)‐mediated responses, mRNA levels and radioligand binding in ileum from β 3 ‐AR knock‐out (−/−) (KO) and wild type (+/+) (FVB) mice. In KO and FVB mice, SR59230A (100 n M ) (β 3 ‐AR antagonist) antagonized responses to (−)‐isoprenaline in both KO and FVB mice. (−)‐Isoprenaline mediated relaxation of ileum was antagonized weakly by ICI118551 (100 n M ) (β 2 ‐AR antagonist). Responses to (−)‐isoprenaline were more strongly antagonized by CGP20712A (100 n M ) (β 1 ‐AR antagonist), propranolol (1 μ M ) (β 1 ‐/β 2 ‐AR antagonist), carvedilol (100 n M ) (non‐specific β‐AR antagonist), and CGP12177A (100 n M ) (β 1 ‐/β 2 ‐AR antagonist) in ileum from KO than in FVB mice. Responses to CL316243 (β 3 ‐AR agonist) in ileum from FVB mice were antagonized by SR59230A (100 n M ) but not by propranolol (1 μ M ) or carvedilol (100 n M ). CL316243 was ineffective in relaxing ileum from KO mice. CGP12177A had no agonist actions in ileum from either KO or FVB mice. β 1 ‐AR mRNA levels were increased 3 fold in ileum from KO compared to FVB mice. This was associated with an increased maximum number of β 1 ‐/β 2 ‐AR binding sites (B max ). β 2 ‐AR mRNA levels were unaffected while no β 3 ‐AR mRNA was detected in KO mice. In mouse ileum, β 3 ‐ARs and to a lesser extent β 1 ‐ARs are the predominant adrenoceptor subtypes mediating relaxation in ileum from FVB mice. In KO mice β 1 ‐ARs functionally compensate for the lack of β 3 ‐ARs, and this is associated with increased β 1 ‐AR mRNA and levels of binding.British Journal of Pharmacology (2001) 132 , 433–442; doi: 10.1038/sj.bjp.0703828