Daunorubicin-induced smooth muscle contraction: involvement of Ca2+ entry mechanism.
The mechanisms of the smooth muscle contractile action of daunorubicin were investigated using guinea-pig aortae, and the involvement of the Ca2+ entry mechanism was compared among different smooth-muscle preparations. In the aorta, daunorubicin showed a concentration-dependent contractile action at concentrations of 10-200 microM. The contractile response to daunorubicin was completely dependent on extracellular Ca2+, but only slightly sensitive to verapamil or nifedipine. Trifluoperazine abolished the contraction by daunorubicin, but no significant effect was noted with amiloride, phentolamine, indomethacin or staurosporine. The order of potency (sensitivity) for daunorubicin-induced smooth muscle contraction was oesophagus = gall bladder = iliac artery > bronchus = aorta, while that of maximum reactivity was iliac artery = aorta > bronchus = oesophagus = gall bladder. In the portal vein, daunorubicin showed no contractile action. Although the smooth muscle contraction induced by daunorubicin was strongly dependent on extracellular Ca2+ in the aorta, iliac artery, bronchus, oesophagus and gall bladder, its sensitivity to verapamil varied among the different smooth muscle preparations, with the sensitivity being iliac artery = gall bladder > bronchus = oesophagus > aorta. These results suggest that daunorubicin has contractile action on various kinds of smooth muscle, mainly via the transplasmalemmal Ca2+ entry mechanism, but the degree of involvement of the voltage-dependent Ca2+ channel differs among the different smooth muscle preparations.
Masui
H
H
Department of Hygiene, Hyogo College of Medicine, Japan.
Wakabayashi
I
I
Yoshimoto
S
S
Sakamoto
K
K
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003630:Daunorubicin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D002121:Calcium Channel Blockers; D014268:Trifluoperazine; D011189:Potassium Chloride; D014700:Verapamil; D002118:Calcium; D003630:Daunorubicin