Norepinephrine- and K+-induced Mn2+-dependent contractions and the dynamics of intracellular Mn2+ changes in dispersed smooth muscle cells from Ca2+-depleted Mn2+-loaded vas deferens of the guinea pig.
The cellular mechanisms of norepinephrine (NE)-induced Mn2+-dependent contractions were investigated in dispersed smooth muscle cells from guinea pig vas deferens by characterizing the effects of NE and K+ on cell length observed by videotape microscopy and on intracellular Mn2+ and Ca2+ concentration ([Mn2+]i and [Ca2+]i) observed by confocal microscopy. Both stimulants induced slow sustained contraction in Ca2+-depleted, Mn2+-accumulated cells (Mn2+-loaded cells), whereas they induced biphasic contractions in normal cells that were neither Ca2+-depleted nor Mn2+-loaded. In both conditions, the number of cells responding to NE as well as the magnitude of NE-induced contractions increased in a dose-dependent manner. Contractions induced by K+ in Mn2+-loaded strip preparations were markedly smaller than those induced by NE. Although individual K+-induced contractions in responsive Mn2+-loaded cells were as large as those induced by NE, a much smaller percentage of Mn2+-loaded cells was responsive to K+ than to NE. These results are consistent with the idea that the contractions of strip preparations may reflect the magnitude of the contractions of individual cells as well as the percentage of responsive cells in the preparations. Inconsistent with the contractions, the [Mn2+]i rise induced by K+ was larger than that induced by NE, and the percentage of cells responsive to K+ was larger than that responsive to NE. These results suggest that NE may increase the Mn2+ sensitivity of contractile elements.
Tsunobuchi-Ushijima
H
H
Department of Pharmacology, Faculty of Pharmaceutical Science, Kanazawa University, Japan.
Ikoma
K
K
Gomi
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D008345:Manganese / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D013997:Time Factors; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D008345:Manganese; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine