Characteristic features of noradrenaline-induced Ca2+ mobilization and tension in arterial smooth muscle of the rabbit.
1. Effects of noradrenaline (NAd) on changes in cellular Ca2+ concentration ([Ca2+]i) and tension were investigated, and these effects were compared with those evoked by 128 mM K+ or caffeine in intact smooth muscle strips or by inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) or caffeine in beta-escin-treated chemically skinned smooth muscle strips of the rabbit mesenteric artery. 2. In physiological solution containing 2.6 mM Ca2+, application of 128 mM K+ or 10 microM NAd produced a phasic, followed by a tonic increase in [Ca2+]i and tension. NAd (10 microM) produced a larger tonic tension than did 128 mM K+ but a smaller increase in [Ca2+]i. When the [Ca2+]i-tension relationship was observed in ionomycin- and 128 mM K(+)-treated muscle strips, 10 microM NAs shifted the relationship to the left and enhanced the maximum amplitude of contraction. These results suggest that NAd increases the sensitivity of contractile proteins to Ca2+ in smooth muscle of the rabbit mesenteric artery. 3. Noradrenaline (10 microM) or caffeine (10 mM), but not 128 mM K+, produced a phasic increase in both [Ca2+]i and tension in Ca(2+)-free solution containing 2 mM EGTA. When 10 mM caffeine had been applied in Ca(2+)-free solution, subsequent application of 10 microM NAd did not increase [Ca2+]i. By contrast, when 10 microM NAd had been applied in Ca(2+)-free solution, subsequent application of 10 mM caffeine still increased [Ca2+]i. Ryanodine (50 microM) abolished the increase in [Ca2+]i induced by 10 mM caffeine or 10 microM NAd in intact and in skinned smooth muscle strips. These results suggest that NAd releases Ca2+ from the ryanodine-sensitive Ca2+ storage sites. 4. Noradrenaline (10 microM) synthesized Ins(1,4,5)P3 in Ca(2+)-free solution in intact smooth muscle strips. Following application of 10 microM NAd, a relatively long time lag (around 1 s) was always observed before the initiation of the increase in [Ca2+]i whether in the presence or absence of Ca2+. The maximum rate of rise of [Ca2+]i induced by 10 mM caffeine was much larger than that induced by 10 microM NAd in Ca(2+)-containing or Ca(2+)-free solution (containing 2 mM EGTA). Both [Ca2+]i and tension reached their peak in a shorter time with caffeine (10 mM) than with 10 microM NAd. In Beta-escin-treated skinned smooth muscle strips, 20 microM Ins(1,4,5)P3 10 mM caffeine or 10 microM NAd increased Ca2+ in Ca(2+)-free solution following brief application of 0.3 microM Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)
Itoh
T
T
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kajikuri
J
J
Kuriyama
H
H
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology
D012433:Ryanodine; D002110:Caffeine; D015759:Ionomycin; D015544:Inositol 1,4,5-Trisphosphate; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine