Functional and molecular evidence for β 1 ‐, β 2 ‐ and β 3 ‐adrenoceptors in human colon

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. β 1 ‐, β 2 ‐ and β 3 ‐Adrenoceptor mRNAs were also measured in colonic muscle and mucosa. (–)‐Isoprenaline caused relaxation of longitudinal smooth muscle preparations with pEC 50 =7.39±0.12, and this response was inhibited by both propranolol (0.1 μ m , p K B 8.55±0.12) and the selective β 1 ‐antagonist, CGP 20712A (0.1 μ m , p K B 8.80±0.20), while the selective β 2 ‐antagonist, ICI 118551 (0.1 μ m ) failed to inhibit isoprenaline relaxation consistently. (–)‐Isoprenaline caused relaxation of taenia coli with a pEC 50 of 6.70±0.17. Propranolol (0.1 μ m ), CGP 20712A (0.1 μ m ) and ICI 118551 (0.1 μ m ) inhibited the isoprenaline response with similar low affinities (p K 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. β 1 ‐ and β 2 ‐Adrenoceptor mRNAs were present in circular/longitudinal muscle samples and taenia coli samples, and lower levels were detected in mucosa. β 3 ‐mRNA was also present in both muscle preparations but was not detected in human colonic mucosa. In summary, β 1 ‐adrenoceptors are the predominant subtype mediating isoprenaline‐induced relaxation of the thin longitudinal smooth muscle of human colon, while β 3 ‐receptors do not appear to be involved in these responses. However, β 3 ‐adrenoceptors may play a role in relaxation of the taenia coli as conventional antagonist affinities are low. β 3 ‐Adrenoceptor mRNA was present in taenia coli and circular/longitudinal smooth muscle but absent from human colonic mucosa.British Journal of Pharmacology (1997) 120 , 1527–1535; doi: 10.1038/sj.bjp.0701056