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 pD(2) 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 pA(2)) 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 pD(2) value being 4.83+/-0.10. On this CCh-induced ureteral relaxation, the rank order of antagonistic potencies (apparent pA(2)) 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 N(omega)-nitro-L-arginine (L-NOARG; 1 x 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.
Tomiyama
Yoshitaka
Y
Central Research Laboratory, Kissei Pharmaceutical Co. Ltd., 4365-1 Kashiwabara, 399-8304 Hotaka, Nagano, Japan. yoshitaka_tomiyama@pharm.kissei.co.jp
Wanajo
Isao
I
Yamazaki
Yoshinobu
Y
Murakami
Makoto
M
Kojima
Masami
M
Shibata
Nobuo
N
D000818:Animals; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D014513:Ureter / Q000502:physiology*
D018679:Cholinergic Agonists; D011976:Receptors, Muscarinic; D011189:Potassium Chloride; D002217:Carbachol