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Ionic currents involved in vasodilating actions of E4080, a newly synthesized bradycardia-inducing agent, in dispersed smooth muscle cells of the rabbit portal vein.

Abstract
The effects of E4080 [(E)-N-[3-[N'-(2-(3,5-dimethoxyphenyl)ethyl)-N'-methyl)amino)propyl]-4- (4-(1H-imidazol-1-yl)phenyl)-3-butenamide dihydrochloride dihydrate] on ionic currents recorded from the rabbit portal vein were investigated by using the patch-clamp technique. A depolarization of the membrane produced an inward Ca current (ICa), a transient outward current (ITO), a sustained outward current (ISO) and an oscillatory outward current (IOO), whereas a hyperpolarization of the membrane produced a hyperpolarization-activated current (Ih). When ICa was evoked by a depolarizing pulse to 0 mV from the holding potential of -80 mV, 1 microM E4080 increased and higher concentrations (10 microM) inhibited ICa, whereas, at the holding potential of -60 mV, E4080 (greater than 1 microM) consistently inhibited ICa, in a concentration-dependent manner. E4080 inhibited ITO, ISO (greater than or equal to 1 microM) and Ih (greater than or equal to 0.1 microM) concentration dependently. Inasmuch as 1 microM E4080 did not inhibit ICa at the holding potential of -80 mV, the inhibition of ITO induced by 1 microM E4080 was not related to the inhibition of ICa. When a continuous depolarization (0 mV) was applied to the cell, E4080 (1 microM) produced a maintained outward current (14.0 +/- 15.3 pA), which was inhibited by glibenclamide. I infinity was inhibited by E4080 (greater than or equal to 0.1 microM) and application of 1 microM glibenclamide partly restored I infinity.(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsM Kamouchi, Z Xiong, N Teramoto, S Kajioka, K Okabe, K Kitamura
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 259 Issue 3 Pg. 1396-403 (Dec 1991) ISSN: 0022-3565 [Print] United States
PMID1762086 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Catechols
  • Imidazoles
  • Solutions
  • Vasodilator Agents
  • E 4080
  • Potassium
  • Calcium
Topics
  • Animals
  • Bradycardia (chemically induced)
  • Calcium (physiology)
  • Catechols (pharmacology)
  • Imidazoles (pharmacology)
  • Male
  • Membrane Potentials (drug effects)
  • Muscle, Smooth, Vascular (cytology, drug effects, physiology)
  • Osmolar Concentration
  • Portal Vein (cytology, drug effects, physiology)
  • Potassium (physiology)
  • Rabbits
  • Solutions
  • Vasodilator Agents (pharmacology)

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