Inhibitory Effects of Potassium Channel Blockers on Carbachol-induced Contraction in Rat Detrusor Muscle.
10.3346/jkms.2003.18.5.701
- Author:
Seung June OH
1
;
Seung Cheol AHN
Author Information
1. Department of Urology, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Rat;
Urinary Tract;
Bladder;
Carbachol;
Tetraethylammonium;
4-Aminopyridine
- MeSH:
4-Aminopyridine/pharmacology;
Animals;
Bladder/metabolism;
Calcium/chemistry/metabolism;
Calcium Channel Blockers/pharmacology;
Carbachol/*pharmacology;
Dose-Response Relationship, Drug;
Female;
Guinea Pigs;
Inhibitory Concentration 50;
Male;
Mice;
Muscle Contraction/*drug effects;
Muscles/drug effects/metabolism/*pathology;
Nicardipine/pharmacology;
Potassium Channel Blockers/*pharmacology;
Protein Binding;
Rabbits;
Rats;
Rats, Sprague-Dawley;
Support, Non-U.S. Gov't;
Tetraethylammonium/pharmacology;
Vasodilator Agents/pharmacology
- From:Journal of Korean Medical Science
2003;18(5):701-706
- CountryRepublic of Korea
- Language:English
-
Abstract:
We present accidental findings that potassium channel blockers, such as tetraethyl-ammonium (TEA) or 4-aminopyridine (4-AP), inhibit the sustained tonic contraction induced by carbachol in rat detrusor muscle strips. The relatively lower concentrations (<2 mM) of TEA and 4-AP inhibited phasic and tonic contractions induced by 5 micrometer carbachol, whilst the relatively higher concentrations of TEA and 4-AP (>5 mM) potentiated phasic contractions. The potentiation of phasic contraction was not observed in nicardipine pretreated condition. In nicardipine pretreated condition, the concentration-response curves for the negative inotropic effect of potassium channel blockers were shifted to the right by the increasing concentration of carbachol from 0.5 micrometer to 5 micrometer. IC50 was changed significantly from 0.19 to 0.64 mM (TEA) and from 0.21 to 0.96 (4-AP). Such inhibitory effects were also observed in Ca2+ depleted condition, where 0.1 mM EGTA and 1 micrometer thapsigargin were added into Ca2+ free solution. In conclusion, inhibitory effects of potasssium channel blockers on carbachol-induced contraction may be ascribed to the direct inhibition of receptor-agonist binding.
