Functional assessment of beta adrenoceptor subtypes in human colonic circular and longitudinal (taenia coli) smooth muscle

Background and aims-The subtype and species related heterogeneity of beta a drenoceptors prompted a functional reappraisal of these molecular targets o f motility inhibition in the human colon. Methods-Relaxation of muscle strips was measured in vitro. Results-The following agonists had decreasing relaxing potency (effective c oncentration range 10(-8)-10(-4) mol/l): (-)isoprenaline (non-selective), t erbutaline (beta(2) selective), CGP 12177 (beta(3) selective, also beta(1), beta(2) antagonist), and SR 58611A (beta(3) selective). Isoprenaline and t erbutaline were more potent on circular than taenia strips; CGP 12177 and S R 58611A weakly and partially relaxed taenia but had little effect on circu lar strips. The potency of isoprenaline on circular strips was greatly redu ced by the beta(1) selective antagonist CGP 20712 (10(-7) mol/l), and less so by ICI 118551 (10(-7) mol/l, beta(2) selective). CGP 20712 and ICI 11855 1 together (both 3x10(-6) mol/l) had no effect on taenia relaxation by SR 5 8611A and rendered isoprenaline and terbutaline virtually inactive on circu lar strips, although not on taenia, which was relaxed at higher than contro l concentrations and maximally by isoprenaline. Propranolol, a beta(1), bet a(2) non-selective antagonist, at high concentrations (10(-5) mol/l) preven ted taenia relaxation by CGP 12177 and SR 586111A; its quantitative antagon ism of isoprenaline tin common with that of CGP 12177 used as an antagonist ) was competitive in circular strips but not on taenia. Conclusions-beta(1) beta(2), and beta(3) adrenoceptors are functionally det ectable in the human colon; agonist stimulation of any one type relaxed tae nia but only isoprenaline was fully effective at the beta(3) subtype.