Inhibition by ouabain and veratridine of acetylcholine-evoked phasic contraction in the guinea-pig taenia coli.
Inhibitory action of ouabain and veratridine on acetylcholine (ACh)-evoked phasic contraction was examined in the guinea-pig taenia coli. ACh (5 x 10(-4)M) produced a biphasic (phasic and tonic) contraction. As the phasic contraction, but not the tonic contraction, was resistant to gallopamil (D600, 2 x 10(-7)M), a blocker of voltage-dependent Ca2+ channels, all experiments were carried out in the presence of gallopamil at this concentration. Addition of high Ca2+ (30 mM) to the solution containing ACh induced a sustained contraction, which increased in the presence of ouabain (10(-5)M), an inhibitor of the Na(+)-K+ exchange system. On the other hand, the ACh-evoked phasic contraction was suppressed by ouabain (10(-7)-10(-5) M) in a time- and dose-dependent manner. The suppression by ouabain (10(-6)M) of the phasic contraction was transiently potentiated by the addition of veratridine (10(-6)M), an activator of Na+ channel. In contrast, the greater suppression by ouabain (10(-5)M) of the contraction was antagonized by amiloride (10(-4)M), a blocker of Na+ channel. This antagonism by amiloride was transiently inhibited in the presence of veratridine. In the absence of ouabain, the amplitude of the phasic contraction was transiently reduced by adding veratridine but was increased by amiloride. In addition, the phasic contraction by ACh increased 80 min after exposure to Na(+)-free isotonic high-K+ solution (K+, 143 mM), which elicited greater depolarization of the cell membrane. In a fluorescence study with Fura-2, an intracellular free-Ca2+ indicator, ACh increased the fluorescence intensity from the tissue by excitative light at 340 nm, which coupled with the phasic contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Usune
S
S
Research Laboratory of Biodynamics, School of Medicine, Fukuoka University, Japan.
Katsuragi
T
T
Furukawa
T
T
D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003106:Colon / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005470:Fluorometry; D016257:Fura-2; D005711:Gallopamil / Q000494:pharmacology; D006168:Guinea Pigs; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D012964:Sodium; D014701:Veratridine / Q000494:pharmacology*
D005711:Gallopamil; D010042:Ouabain; D014701:Veratridine; D000584:Amiloride; D012964:Sodium; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D016257:Fura-2