Comparison of the in vitro effects of K+ channel modulators on detrusor and portal vein strips from guinea pigs.
The effects of K+ channel openers and blockers on smooth muscles of vascular and nonvascular origin from guinea pigs have been investigated. Cromakalim, pinacidil, nicorandil and minoxidil sulfate all abolished the spontaneous myogenic activity of the guinea pig portal vein and the KCl-evoked activity of detrusor strips with the same rank order of ptoency. Whereas both apamin and charybdotoxin stimulated myogenic activity of the detrusor strips, they produced insignificant effects on spontaneously active portal vein strips and failed to antagonize the mechanoinhibitory effects of cromakalim in the two tissues. Glibenclamide, on the other hand, only stimulated the myogenic activity of portal vein strips but antagonized the mechanoinhibitory effects of cromakalim, pinacidil, nicorandil and minoxidil sulfate in both tissues. Rubidium, at millimolar concentrations, stimulated the myogenic activity, and antagonized the actions of cromakalim in both tissues. The data indicate that there are definite functional dissimilarities as exhibited by the differential response of the two tissues to K+ channel modulators. These findings may be exploited in the design of new drugs with tissue selectivity.
Zografos
P
P
Department of Pharmacology, ICI Pharmaceuticals Group, Wilmington, Del. 19897.
Li
J H
JH
Kau
S T
ST
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008914:Minoxidil / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D020110:Pinacidil; D011169:Portal Vein / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D008914:Minoxidil; D011189:Potassium Chloride; D020110:Pinacidil; D005905:Glyburide