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Biomedical subjects

Shigeru Hishinuma

Publications and source records attributed to Shigeru Hishinuma.

6 recordsLinked to original sources
PubMed2006

Differential roles of ryanodine- and thapsigargin-sensitive intracellular CA2+ stores in excitation-contraction coupling in smooth muscle of guinea-pig taenia caeci.

1. To explore roles of intracellular Ca(2+) stores in excitation-contraction coupling in smooth muscle, we examined the effects of ryanodine, a fixer of ryanodine receptor-Ca(2+) channels to an open state, and thapsigargin, a selective inhibitor of the Ca(2+) pump in the intracellular stores, on smooth muscle contraction in the presence and absence of extracellular Ca(2+) in guinea-pig taenia caeci. 2. In Ca(2+) -free solution, contractions induced by 0.1 mmol/L carbachol and 0.1 mmol/L histamine were reduced to approximately 65% of control by either 1 micro mol/L thapsigargin or 10 micro mol/L ryanodine. In contrast, caffeine-induced contraction was reduced to approximately 40% of control by ryanodine, but was not affected by thapsigargin. 3. In the presence of extracellular Ca(2+), thapsigargin slowly induced a large and sustained contraction. In contrast, ryanodine did not induce an apparent contraction, but increased the sensitivity of contractile responses to receptor agonists (carbachol, AHR-602 and histamine) or depolarizing high K(+) with no changes in the maximal contraction. 4. These results suggest that there are pharmacological and physiological differences between ryanodine- and thapsigargin-sensitive intracellular Ca(2+) stores in excitation-contraction coupling in smooth muscle, which may be responsible for their differential effects on the Ca(2+) -influx pathway.

Animals↗
PubMed2002

Membrane depolarization-induced contraction of rat caudal arterial smooth muscle involves Rho-associated kinase.

Depolarization of the sarcolemma of smooth muscle cells activates voltage-gated Ca2+ channels, influx of Ca2+ and activation of cross-bridge cycling by phosphorylation of myosin catalysed by Ca2+/calmodulin-dependent myosin light-chain kinase (MLCK). Agonist stimulation of smooth muscle contraction often involves other kinases in addition to MLCK. In the present study, we address the hypothesis that membrane depolarization-induced contraction of rat caudal arterial smooth muscle may involve activation of Rho-associated kinase (ROK). Addition of 60 mM K+ to de-endothelialized muscle strips in the presence of prazosin and propranolol induced a contraction that peaked rapidly and then declined to a steady level of force corresponding to approx. 30% of the peak contraction. This contractile response was abolished by the Ca2+-channel blocker nicardipine or the removal of extracellular Ca2+. An MLCK inhibitor (ML-9) inhibited both the phasic and tonic components of K+-induced contraction. On the other hand, the ROK inhibitors Y-27632 and HA-1077 abolished the tonic component of K+-induced contraction, and slightly reduced the phasic component. Phosphorylation levels of the 20-kDa light chain of myosin increased rapidly in response to 60 mM K+ and subsequently declined to a steady-state level significantly greater than the resting level. Y-27632 abolished the sustained and reduced the phasic elevation of the phosphorylation of the 20-kDa light chain of myosin, without affecting the K+-induced elevation of cytosolic free Ca2+ concentration. These results indicate that ROK activation plays an important role in the sustained phase of K+-induced contraction of rat caudal arterial smooth muscle, but has little involvement in the phasic component of K+-induced contraction. Furthermore, these results are consistent with inhibition of myosin light-chain phosphatase by ROK, which would account for the sustained elevation of myosin phosphorylation and tension in response to membrane depolarization.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2002

Cloning and characterization of novel snake venom proteins that block smooth muscle contraction.

In this study, we isolated a 25-kDa novel snake venom protein, designated ablomin, from the venom of the Japanese Mamushi snake (Agkistrodon blomhoffi). The amino-acid sequence of this protein was determined by peptide sequencing and cDNA cloning. The deduced sequence showed high similarity to helothermine from the Mexican beaded lizard (Heloderma horridum horridum), which blocks voltage-gated calcium and potassium channels, and ryanodine receptors. Ablomin blocked contraction of rat tail arterial smooth muscle elicited by high K+-induced depolarization in the 0.1-1 microm range, but did not block caffeine-stimulated contraction. Furthermore, we isolated three other proteins from snake venoms that are homologous to ablomin and cloned the corresponding cDNAs. Two of these homologous proteins, triflin and latisemin, also inhibited high K+-induced contraction of the artery. These results indicate that several snake venoms contain novel proteins with neurotoxin-like activity.

Agkistrodon↗
PubMedDate not supplied

Ca2+-dependent differential development of carbachol-induced desensitization to receptor agonists and high K+ in guinea-pig taenia caeci.

1. Carbachol (CCh)-induced desensitization to CCh was interrupted by a transient resensitization during its early stage, with concomitant changes at the muscarinic receptor/G-protein level in smooth muscle of guinea-pig taenia caeci. To assess whether such a peculiar desensitizing process may heterologously regulate smooth muscle contraction, we examined the developmental processes of CCh-induced desensitization to histamine and high K(+) and compared it with that to CCh. 2. Under Ca(2+)-containing physiological conditions, treatment with 10(-4) mol/L CCh for 30 min induced heterologous desensitization to histamine and high K(+). The development of desensitization to histamine was interrupted by a transient resensitization at 1 min in a manner similar to that to CCh. In contrast, CCh-induced desensitization to high K(+) reached a peak at 1 min and was followed by a gradual resensitization up to a partial restoration at 30 min. 3. Under Ca(2+)-free conditions containing 0.2 mmol/L EGTA, treatment with 10(-4) mol/L CCh for 30 min failed to induce heterologous desensitization to either histamine or high K(+), whereas the CCh treatment developed homologous desensitization to CCh in a simple time-dependent manner without a resensitization phase. 4. These results suggest that cellular responsiveness to receptor agonists and non-receptor-mediated depolarizing stimulation is differentially regulated by Ca(2+)-dependent heterologous desensitization in smooth muscle.

Animals↗