Functional and molecular evidence for β₁-, β₂- and β₃-adrenoceptors in human colon

1. Relaxation of carbachol pre-contracted human colonic muscle to (-)-isoprenaline was examined in circular, longitudinal and taenia coli preparations to determine the β-adrenoceptor subtypes involved. β₁-, β₂- and β₃-Adrenoceptor mRNAs were also measured in colonic muscle and mucosa. 2. (-)-Isoprenaline caused relaxation of longitudinal smooth muscle preparations with pEC₅₀ = 7.39 ± 0.12, and this response was inhibited by both propranolol (0.1 μM, pK(B) 8.55 ± 0.12) and the selective β₁-antagonist, CGP 20712A (0.1 μM, pK(B) 8.80 ± 0.20), while the selective β₂-antagonist, ICI 118551 (0.1 μM) failed to inhibit isoprenaline relaxation consistently. 3. (-)-Isoprenaline caused relaxation of taenia coli with a pEC₅₀ of 6.70 ± 0.17. Propranolol (0.1 μM), CGP 20712A (0.1 μM) and ICI 118551 (0.1 μM) inhibited the isoprenaline response with similar low affinities (pK(B) values 7.93, 7.71 and 7.54, respectively). Carbachol pre-contracted circular smooth muscle preparations failed to relax consistently to isoprenaline and these responses were not characterized. 4. β₁- and β₂-Adrenoceptor mRNAs were present in circular/longitudinal muscle samples and taenia coli samples, and lower levels were detected in mucosa. β₃-mRNA was also present in both muscle preparations but was not detected in human colonic mucosa. 5. In summary, β₁-adrenoceptors are the predominant subtype mediating isoprenaline-induced relaxation of the thin longitudinal smooth muscle of human colon, while β₃-receptors do not appear to be involved in these responses. However, β₃-adrenoceptors may play a role in relaxation of the taenia coli as conventional antagonist affinities are low. β₃-Adrenoceptor mRNA was present in taenia coli and circular/longitudinal smooth muscle but absent from human colonic mucosa.