Functional muscarinic cholinoceptors in the isolated canine ureter.

The purpose of present study was to characterize the functional muscarinic cholinoceptor (mAChR) subtypes in the isolated canine ureter. Carbachol (CCh), a non-selective mAChR agonist, concentration-dependently increased the frequency of the rhythmic contractions in isolated spiral ureteral preparations, the pD2 value being 5.78±0.12. We then evaluated the effects of subtype-selective mAChR antagonists on the CCh-induced rhythmic contractions. The rank order of antagonistic potencies (apparent pA2) was 4-diphenylacetoxy-N-methylpiperidinemethiodide (4-DAMP; M3-subtype selective; 9.31±0.06) >atropine (non-selective; 9.16±0.10) >himbacine (M4-subtype selective; 7.32±0.18) >pirenzepine (M1-subtype selective; 6.78±0.16) >methoctramine (M2-subtype selective; 5.51±0.43). In sharp contrast, CCh concentration-dependently reduced the 80 mM KCl-induced contraction in longitudinal ureteral preparations, the pD2 value being 4.83±0.10. On this CCh-induced ureteral relaxation, the rank order of antagonistic potencies (apparent pA2) was atropine (8.56±0.09) >4-DAMP (7.63±0.21) >himbacine (7.46±0.09) >methoctramine (6.54±0.18) >pirenzepine (6.33±0.22). The nitric-oxide-synthase inhibitor Nω-nitro-L-arginine (L-NOARG; 1×10−4 M) had no effect on the CCh-induced ureteral relaxation. These data suggest that the CCh-induced rhythmic contraction in the spiral preparation was mediated via the M3-receptor, while the CCh-induced relaxation in the longitudinal preparation was probably mediated mainly via the M4-receptor.