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

Background and aims—The subtype and species related heterogeneity of â adrenoceptors prompted a functional reappraisal of these molecular targets of motility inhibition in the human colon. Methods—Relaxation of muscle strips was measured in vitro. Results—The following agonists had decreasing relaxing potency (eVective concentration range 10–10 mol/l): (−)isoprenaline (non-selective), terbutaline (â2 selective), CGP 12177 (â3 selective, also â1, â2 antagonist), and SR 58611A (â3 selective). Isoprenaline and terbutaline were more potent on circular than taenia strips; CGP 12177 and SR 58611A weakly and partially relaxed taenia but had little eVect on circular strips. The potency of isoprenaline on circular strips was greatly reduced by the â1 selective antagonist CGP 20712 (10 mol/l), and less so by ICI 118551 (10 mol/l, â2 selective). CGP 20712 and ICI 118551 together (both 3×10 mol/l) had no eVect on taenia relaxation by SR 58611A and rendered isoprenaline and terbutaline virtually inactive on circular strips, although not on taenia, which was relaxed at higher than control concentrations and maximally by isoprenaline. Propranolol, a â1, â2 non-selective antagonist, at high concentrations (10 mol/l) prevented taenia relaxation by CGP 12177 and SR 58611A; its quantitative antagonism of isoprenaline (in common with that of CGP 12177 used as an antagonist) was competitive in circular strips but not on taenia. Conclusions—â1, â2, and â3 adrenoceptors are functionally detectable in the human colon; agonist stimulation of any one type relaxed taenia but only isoprenaline was fully eVective at the â3 subtype. (Gut 2000;47:337–342)