Discrimination by nimodipine, but not by nifedipine, between phasic and tonic contractions of guinea-pig taenia coli induced by K+ depolarization.
Effects of Ca2+ channel blockers, such as nifedipine, nimodipine, gallopamil, verapamil, diltiazem, loperamide, Mn2+ and Ni2+, and papaverine, on contractile responses to K+ depolarization were evaluated in longitudinal muscles of taenia coli isolated from guinea-pig. Depolarization with high K+ solution (K+, 40 mM) produced a biphasic (phasic and tonic) contraction, which was inhibited by the above blockers in a concentration-dependent manner. Ratios of IC50 for the phasic contraction to IC50 for the tonic contraction of nimodipine, verapamil, gallopamil, nifedipine, loperamide, diltiazem, papaverine, Ni2+, and Mn2+ were 516.1, 73.7, 22.0, 6.4, 5.3, 4.9, 1.2, 0.7, and 0.1, respectively, indicating that nimodipine suppressed the tonic contraction more effectively than the phasic contraction. In a fluorescence study with fura 2, K+ depolarization elicited an increase in intracellular free Ca2+, [Ca2+]i, which was coupled with the phasic and tonic contraction. The increases in [Ca2+]i coupled with both types of the contraction were abolished by exposure to Ca(2+)-free solution. In addition, the increase of [Ca2+]i coupled with the phasic contraction was abolished by nifedipine, 10(-7) M, but not by nimodipine, 10(-7) M, whereas the increase with the tonic contraction was suppressed by both nifedipine and nimodipine. These findings suggest that the phasic and tonic contractions evoked by K+ depolarization are due to increases in [Ca2+]i via activation of respective nimodipine-resistant and nimodipine-sensitive Ca2+ channels in the longitudinal muscles of the taenia coli. Accordingly, nimodipine, but not nifedipine, appears to be a useful tool for distinguishing between the phasic and tonic contractions.
Usune
S
S
Research Laboratory of Biodynamics, Fukuoka University, Japan.
Katsuragi
T
T
Furukawa
T
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006982:Hypertonic Solutions; D066298:In Vitro Techniques; D008297:Male; D008345:Manganese / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009467:Neuromuscular Depolarizing Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology*; D011188:Potassium / Q000037:antagonists & inhibitors / Q000494:pharmacology
D002121:Calcium Channel Blockers; D006982:Hypertonic Solutions; D009467:Neuromuscular Depolarizing Agents; D008345:Manganese; D009553:Nimodipine; D009543:Nifedipine; D011188:Potassium