Mechanical and electrophysiological effects of cromakalim on the human urinary bladder.
The effects of cromakalim on spontaneous and induced mechanical activity of human detrusor muscle were investigated in vitro. Cromakalim produces a concentration-related decrease of spontaneous as well as carbachol- and K(+)-evoked contractions. This is the first study to utilize the patch clamp technique to elucidate the mechanism of action of cromakalim on human detrusor cells. Cromakalim hyperpolarizes the detrusor cells by increasing the net outward current which is most likely carried by potassium ions. In the human urinary bladder, this effect is mediated by a glibenclamide-sensitive potassium channel, as glibenclamide is able to diminish the relaxant effect of cromakalim and to prevent the drug-induced hyperpolarization. Our results show that the effectiveness of cromakalim in relaxing the detrusor muscle is about an order of magnitude higher in the rat and guinea pig than in humans. It is therefore deemed unlikely that cromakalim or drugs with the same mode of action and similar tissue specificity will be of value in the clinical treatment of bladder instability and hyperreflexia. Moreover, it is suggested that when studies are undertaken to elucidate the effects and clinical potential of new drugs acting upon the bladder, human detrusor tissue should be used. The rat and guinea pig are unsuitable for this purpose.
Department of Urology, University of Mainz, FRG.
R
R
Wammack
U
U
Jahnel
H
H
Nawrath
R
R
Hohenfellner
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010276:Parasympatholytics / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D001578:Benzopyrans; D010276:Parasympatholytics; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim