title: Ca2+-dependent modulation of intracellular Mg2+ concentration with amiloride and KB-R7943 in pig carotid artery.
abstract: It has long been recognized that magnesium is associated with several important diseases, including diabetes, hypertension, cardiovascular, and cerebrovascular diseases. In the present study, we measured the intracellular free Mg2+ concentration ([Mg2+]i) using 31P nuclear magnetic resonance (NMR) in pig carotid artery smooth muscle. In normal solution, application of amiloride (1 mm) decreased [Mg2+]i by approximately 12% after 100 min. Subsequent washout tended to further decrease [Mg2+]i. In contrast, application of amiloride significantly increased [Mg2+]i (by approximately 13% after 100 min) under Ca2+-free conditions, where passive Mg2+ influx is facilitated. The treatments had little effect on intracellular ATP and pH (pHi). Essentially the same Ca2+-dependent changes in [Mg2+]i were produced with KB-R7943, a selective blocker of reverse mode Na+-Ca2+ exchange. Application of dimethyl amiloride (0.1 mM) in the presence of Ca2+ did not significantly change [Mg2+]i, although it inhibited Na+-H+ exchange at the same concentration. Removal of extracellular Na+ caused a marginal increase in [Mg2+]i after 100-200 min, as seen in intestinal smooth muscle in which Na+-Mg2+ exchange is known to be the primary mechanism of maintaining a low [Mg2+]i against electrochemical equilibrium. In Na+-free solution (containing Ca2+), neither amiloride nor KB-R7943 decreased [Mg2+]i, but they rather increased it. The results suggest that these inhibitory drugs for Na+-Ca2+ exchange directly modulate Na+-Mg2+ exchange in a Ca2+-dependent manner, and consequently produce the paradoxical decrease in [Mg2+]i in the presence of Ca2+.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Uetani
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Matsubara
authors.forename: Hideki
authors.initials: H
authors.lastname: Nomura
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakayama
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D002339:Carotid Arteries / Q000378:metabolism*; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009130:Muscle, Smooth / Q000378:metabolism; D012964:Sodium / Q000737:chemistry; D013552:Swine; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000889:Anti-Arrhythmia Agents; D004232:Diuretics; D000584:Amiloride; D000255:Adenosine Triphosphate; D012964:Sodium; D013890:Thiourea; D008274:Magnesium; D002118:Calcium