Mechanism of potentiation by tea epigallocatechin of contraction in porcine coronary artery: the role of protein kinase Cδ-mediated CPI-17 phosphorylation.

The effects of green tea catechins, (+)- and (-)-catechins (C), (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin (EGC), and (-)-epigallocatechin gallate (EGCG), on vascular contractility were investigated in porcine coronary artery. At the concentration of 200 μM, only EGC, but not other catechins, potentiated high K(+)-induced contraction in a concentration-dependent manner, although EGC by itself did not produce contraction. The potentiator effect of EGC was still observed in endothelium-denuded preparations.

Interactive role of protein phosphatase 2A and protein kinase Calpha in the stretch-induced triphosphorylation of myosin light chain in canine cerebral artery.

The interactive role of protein kinase C (PKC) isoforms and protein phosphatase 2A (PP2A) in the mechanisms underlying the gradual reduction in stretch-induced contraction through triphosphorylation of 20-kDa myosin light chain (MLC(20)) was investigated in the canine basilar artery. In the presence of 5 mM tetraethylammonium, stretching at a rate of 1 mm/s from the initial length (L(i)) to 1.5 L(i) produced a contraction.

The relaxant effect of okadaic acid on canine basilar artery involves activation of PKCalpha and phosphorylation of the myosin light chain at Thr-9.

Vasodilator responses induced by okadaic acid were investigated in canine basilar artery precontracted with 80 mM KCl. Okadaic acid (1 microM) relaxed the artery and this relaxant effect was partially inhibited by Gö6976, a conventional protein kinase C inhibitor, and calphostin C, an inhibitor of conventional and novel PKCs. Rottlerin, a specific inhibitor of PKCdelta, did not influence okadaic acid's effect.

Stretch-induced triphosphorylation of myosin light chain and myogenic tone in canine basilar artery.

The relationship between phosphorylation of 20,000 Da myosin light chain (MLC20) and contraction in response to mechanical stretch was investigated in the canine basilar artery. A slow stretch (at a rate of 1 mm/s and a stimulus period for 15 min) increased triphosphorylated MLC20 despite lowered intracellular calcium concentration and mechanical activities, such as myogenic tone, shortening velocity and stiffness of the artery. Nicardipine, a Ca2+ channel blocker, and ML-9, a myosin light chain kinase (MLCK) inhibitor, partially inhibited the stretch-induced MLC20 phosphorylation.

Passive stretching produces Akt- and MAPK-dependent augmentations of GLUT4 translocation and glucose uptake in skeletal muscles of mice.

Muscle contraction is accompanied by passive stretching or deformation of cells and tissues. The present study aims to clarify whether or not acute passive stretching evokes glucose transporter 4 (GLUT4) translocation and glucose uptake in skeletal muscles of mice. Passive stretching mainly induced GLUT4 translocation from an intracellular membrane-rich fraction (PF5) to a plasma membrane-rich fraction (F2) and accelerated glucose uptake in hindlimb muscles; whereas electrical stimulation, which mimics physical exercise in vivo, and insulin, each induced GLUT4 translocation from an intracellular membrane-rich fraction (PF5) to a fraction rich in plasma membrane (F2), and to one rich in transverse tubules (PF3), along with subsequent glucose uptake.

Involvement of novel protein kinase C isoforms in carbachol-stimulated insulin secretion from rat pancreatic islets.

The roles of protein kinase C (PKC) isoforms in cholinergic potentiation of glucose-induced insulin secretion were investigated in rat pancreatic islets. Western-blot analysis showed the presence of PKC-alpha, betaII, delta, epsilon, eta, and zeta, but not PKC-betaI, gamma, or iota, in the islets. Carbachol (CCh) caused translocations of PKC-alpha, betaII, delta, and epsilon from the cytosol to the plasma membrane.

Differential interplay between protein kinase C and Rho-kinase in the endothelin-1-induced and pressure-induced contractions of rat posterior cerebral artery.

To clarify the involvement of protein kinase C and Rho-kinase in the contractile activation of cerebral artery in response to endothelin-1 and pressurization, rat posterior cerebral artery (outer diameter, 100-200 microm) was mounted in arteriograph, and the changes in cytosolic Ca2+ and vessel diameter were measured by video-microscopy in connection with an Argus 50 system. Endothelin-1 (10 nM) induced a tonic contraction with a slight increase in cytosolic Ca2+, which was mostly dependent on protein kinase C (chelerythrine sensitive). Intraluminal pressurization (60 mmHg) also produced contraction with a low cytosolic Ca2+, which was myogenic in nature and dependent on both protein kinase C and Rho-kinase (Y-27632 sensitive).

Interactive role of protein kinase C-delta with rho-kinase in the development of cerebral vasospasm in a canine two-hemorrhage model.

Background: We previously reported that protein kinase C (PKC)-delta was initially translocated from the cytosol to the membrane fraction (on day 4), followed by PKC-alpha, with the progression of cerebral vasospasm after subarachnoid hemorrhage (SAH) on day 7. Rho/Rho-kinase pathways have also been proposed to be involved in the vasospasm. Thus we investigated the interactive role of Rho-kinase and PKC in the development of cerebral vasospasm after SAH.

Ionic mechanism for contractile response to hyposmotic challenge in canine basilar arteries.

A hyposmotic challenge elicited contraction of isolated canine basilar arteries. The contractile response was nearly abolished by the removal of extracellular Ca(2+) and by the voltage-dependent Ca(2+) channel (VDCC) blocker nicardipine, but it was unaffected by thapsigargin, which depletes intracellular Ca(2+) stores. The contraction was also inhibited by Gd(3+) and ruthenium red, cation channel blockers, and Cl(-) channel blockers DIDS and niflumic acid.

[Mechanical stress and cerebrovascular response--resemblance to cerebral vasospasm after subarachnoid hemorrhage].

The autoregulatory mechanism, including myogenic response, so-called "Bayliss effect", is well developed in the brain circulatory area, where also, cerebral vasospasm is often encountered after subarachnoid hemorrhage. In the cerebral artery smooth muscle, protein kinases, such as Rho-associated kinase, tyrosine kinase, and protein kinase C, are activated in response to mechanical stresses, including stretch, pressure and flow. All of these kinases are also activated in due course of time after development of the vasospasm.

Evidence for protein kinase C-mediated activation of Rho-kinase in a porcine model of coronary artery spasm.

Objective: We have recently demonstrated that protein kinase C (PKC) and Rho-kinase play important roles in coronary vasospasm in a porcine model. However, it remains to be examined whether there is an interaction between the two molecules to cause the spasm.

Methods And Results: A segment of left porcine coronary artery was chronically treated with IL-1beta-bound microbeads in vivo.

Attenuation of canine cerebral vasospasm after subarachnoid hemorrhage by protein kinase C inhibitors despite augmented phosphorylation of myosin light chain.

The purpose of the present study is to assess the roles of protein kinase C (PKC) isoforms, especially PKC delta and alpha, and 20-kD myosin light chain (MLC(20)) phosphorylation in the mechanism of cerebral vasospasm following subarachnoid hemorrhage (SAH). We had shown that those PKC isoforms are involved in the development of cerebral vasospasm. Using PKC isoform-specific inhibitors in a 'two- hemorrhage' canine model, we examined changes in the development of cerebral vasospasm, translocation of PKC isoforms and MLC(20) phosphorylation level in canine basilar arteries.

[Regulatory role of mechanical stress response in cellular function: development of new drugs and tissue engineering].

The investigation of mechanotransduction in the cardiovascular system is essentially important for elucidating the cellular and molecular mechanisms involved in not only the maintenance of hemodynamic homeostasis but also etiology of cardiovascular diseases including arteriosclerosis. The present review summarizes the latest research performed by six academic groups, and presented at the 75th Annual Meeting of the Japanese Pharmacological Society. Technology of cellular biomechanics is also required for research and clinical application of a vascular hybrid tissue responding to pulsatile stress.

20-Hydroxyeicosatetraenoic acid potentiates stretch-induced contraction of canine basilar artery via PKC alpha-mediated inhibition of KCa channel.

1. The present study was undertaken to elucidate whether PKCalpha plays a role in the mechanism of the stretch-induced contraction potentiated by 20-hydroxyeicosatetraenoic acid (20-HETE). The effects of 20-HETE on the canine basilar artery were compared with those of iberiotoxin, a blocker of large conductance Ca(2+)-activated K(+) channels (K(Ca) channels), as this blocker was shown earlier to sensitize these arteries to mechanical stretch.

Interactive role of tyrosine kinase, protein kinase C, and Rho/Rho kinase systems in the mechanotransduction of vascular smooth muscles.

Blood vessels are always subjected to hemodynamic stresses including blood pressure and blood flow. The cerebral artery is particularly sensitive to hemodynamic stresses such as pressure and stretch, and shows contractions that are myogenic in nature; i.e.

[Role of protein kinase C isozymes in cellular functions and pathological conditions].

Protein kinase C (PKC) is a superfamily of lipid-dependent protein Ser/Thr kinases consisting of at least 10 isozymes. The present article summarizes the papers presented at the congress symposium of the 74th Annual Meeting of the Japanese Pharmacological Society, in which six special topics regarding PKC isozyme-dependent cellular functions and pathological disorders were discussed. Using a GFP-tagged PKC expression technique, each PKC subtype was suggested to vary its targeting-site in each cell in response to each stimulus and that the targeting to the specific compartment is necessary for the specific cellular responses (NS).