8-(Diethylamino)-octyl-3,4,5-trimethoxybenzoate inhibits cromakalim-induced 86Rb efflux from the rat aorta.
The effects of 8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8) on cromakalim-induced 86Rb efflux and vasorelaxation in the rat aorta have been assessed. TMB-8 inhibited cromakalim (10 microM)-induced 86Rb efflux with an IC50 of 0.50 +/- 0.15 microM (n = 4; IC50 for glyburide 0.17 +/- 0.05 microM, n = 4), but it produced minimal antagonism of the cromakalim-induced vasorelaxation (rings precontracted with 30 mM KCl-PSS) at TMB-8 concentrations < or = 3 microM. TMB-8 at 10 microM produced significant inhibition of the cromakalim-induced vasodilation. Inhibition of cromakalim-induced 86Rb efflux produced by TMB-8 was little affected by raising the KCl concentration to 30 mM (inhibition by 0.5 microM TMB-8: 62.9 +/- 6.9 and 52.5 +/- 10.9% in 4.6 and 30 mM KCl, respectively; n = 4 for both). Similarly, the inhibitory effects of glyburide on the cromakalim-induced 86Rb efflux were minimally affected by this maneuver. TMB-8 was approximately equipotent against the increase in 86Rb efflux generated by either 1 or 10 microM cromakalim (IC50: 0.73 +/- 0.11 and 0.65 +/- 0.33 microM, respectively; n = 4 of both). In contrast, the glyburide IC50 was reduced approximately 10-fold by reducing the concentration of cromakalim used from 10 to 1 microM (IC50: 182.5 +/- 4.8 and 19.5 +/- 2.6 nM, respectively; n = 4 for both). We hypothesize that TMB-8 inhibits the potassium channel that is opened by cromakalim.(ABSTRACT TRUNCATED AT 250 WORDS)
Lodge
N J
NJ
Cardiovascular and Metabolic Disorders, Wyeth-Ayerst Research, Princeton, New Jersey.
Halaka
N N
NN
D000818:Animals; D001011:Aorta; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D019806:Cromakalim; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012413:Rubidium / Q000378:metabolism*
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D011189:Potassium Chloride; D012413:Rubidium; D005905:Glyburide