Nasu T, Sasaki M
Department of Veterinary Pharmacology, Faculty of Agriculture, Yamaguchi University, Japan.
J Pharm Pharmacol. 1998 Apr;50(4):437-42. doi: 10.1111/j.2042-7158.1998.tb06885.x.
Mn2+ has been shown to inhibit K+-induced contraction of smooth-muscle, to induce contraction of smooth-muscle in Ca2+-free, K+ medium and to activate the contractile proteins of skinned fibres of smooth muscle cells. Further work has suggested that Mn2+ penetrates the cytoplasm through voltage-dependent Ca2+ channels when the cell membranes of smooth muscles are depolarized with K+. We have investigated whether in Ca2+-free medium, Mn2+ enters the cytoplasm through Ca2+ channels and induces contraction of guinea-pig taenia coli in the presence of Bay K 8644, a dihydropyridine Ca2+-channel agonist which prolongs the open state of the voltage-dependent Ca2+ channels in smooth-muscle cells. In Ca2+-free medium the application of 5 mM Mn2+ in the presence of Bay K 8644 caused contraction of and concomitant increase in Mn2+ uptake in guinea-pig taenia coli smooth muscle. In the presence of Bay K 8644 nifedipine, a dihydropyridine Ca2+ channel antagonist, dose-dependently inhibited both manganese uptake and the contraction induced by Mn2+. These results suggest that Mn2+ enters the cytoplasm through dihydropyridine-sensitive, voltage-dependent Ca2+ channels activated by Bay K 8644 and then induces contraction in taenia coli.
