Functional role of ryanodine-sensitive Ca2+ stores in acidic pH-induced contraction in Wistar Kyoto rat aorta.
Acidic pH induced a contraction in the isolated aorta from Wistar Kyoto rat. The magnitude of contraction was dependent upon the degree of extracellular acidification. The maximum level of contraction observed at pH 6.5 was 84.6 +/- 3.4% of the 64.8 mM KCl-induced contraction. To investigate the role of extracellular as well as intracellular Ca(2+) in acidic pH-induced contraction (APIC), we changed the extracellular pH in the presence of EGTA. Sustained contraction induced by acidic pH in the presence of extracellular Ca(2+) was completely abolished in the presence of EGTA, while a transient but significant contraction was still observed. Ryanodine, a selective ryanodine receptor blocker and cyclopiazonic acid (CPA), an inhibitor of sarco-/endoplasmic reticulum Ca(2+) ATPase, abolished the transient contraction, when pH was decreased in Ca(2+)-free solution. On the other hand, neither xestospongin C, a selective inositol-1,4,5-trisphosphate receptor antagonist nor U-73122, a phospholipase C inhibitor showed this effect. These results suggest the involvement of Ca(2+) release from ryanodine-/CPA-sensitive store of sarcoplasmic reticulum (SR). In normal Ca(2+)-containing solution, ryanodine and CPA did not alter the maximum level of APIC. However, they significantly decreased the rate of rise of APIC. U-73122, suppressed the maximum contraction induced by acidic pH without affecting the rate of rise of APIC, while xestospongin C and U-73343, an inactive analogue of U-73122, had no effect on both parameters of APIC. From these results, it is concluded that acidic pH induces Ca(2+) release from the ryanodine-/CPA-sensitive store of SR and that release provides supportive effect on initiating rapid transient contraction, but not on the sustained contraction, which is entirely due to Ca(2+) influx.
Rohra
Dileep Kumar
DK
Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aoba-ku, Aramaki, Sendai, 980-8578, Japan.
Saito
Shin-ya
SY
Ohizumi
Yasushi
Y
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D004963:Estrenes / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000494:pharmacology; D047028:Macrocyclic Compounds; D008297:Male; D010080:Oxazoles / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D012433:Ryanodine / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D004963:Estrenes; D007211:Indoles; D047028:Macrocyclic Compounds; D010080:Oxazoles; D011760:Pyrrolidinones; C108644:xestospongin A; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D012433:Ryanodine; D002118:Calcium; C000543:cyclopiazonic acid