Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of substrate condition and ADP beta S on the pCa2+-tension relationships were investigated, using alpha-toxin permeabilized rabbit mesenteric artery at 37 degrees C. The contraction induced by 10 microM Ca2+ solution after permeabilization was as large as that induced by 145 mM K+ PSS solution containing 10 microM NE in the intact tissue, indicating that the majority of the cells were permeabilized. The Ca2+ sensitivity was greatly affected by the substrate condition and increasing the ratio of ATP/CP induced a leftward shift of the pCa2+-tension curve. Addition of 100 microM ADP beta S had a similar effect. When the ATP/CP ratio was high, the 0.1 microM Ca2+ solution relaxed the tissue precontracted by 10 microM Ca2+ solution more slowly showing hysteresis. One mM vanadate, which is reported to relax muscle by forming actomyosin-ADP-Vi (AM-ADP-Vi), completely inhibited both contractions induced by 0.18 microM Ca2+ solution containing 2 mM MgADP and 0.3 microM Ca2+ solution containing 0.3 microM PDBu. These results indicated that the population of AM-ADP complex in the crossbridge had increased due to the accumulation of ADP inside the tissue or activation of PKC and that the inhibition of ADP release from AM-ADP complex may be playing a key role in increasing Ca2+ sensitivity of myofilaments.
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PMID:Possible involvement of actomyosin ADP complex in regulation of Ca2+ sensitivity in alpha-toxin permeabilized smooth muscle. 259 Feb 38

1. We examined the effects of ethanol on the contractility of strips of porcine coronary artery, with and without endothelium, and following permeabilization with alpha-toxin, and of aortic valvular endothelial cells, in situ. Changes in cytosolic Ca2+ concentration ([Ca2+]i) of the coronary artery smooth muscle cells and of the valvular endothelial cells were monitored using front-surface fluorometry of the calcium indicator dye, fura-2. In permeabilized preparations, [Ca2+]i was clamped using 10 mM ethyleneglycol-bis-(beta-aminoethylether)-N,N,N',N'-tetra ace tic acid (EGTA) and 10 microM A23187 (a calcium ionophore). 2. The strips without endothelium were placed in normal physiological salt solution (normal PSS) in the presence of ethanol (100-1000 mM). There were dose-dependent increases in [Ca2+]i and a rapid sustained rise in tension. In Ca(2+)-free PSS, ethanol increased [Ca2+]i and tension, similar to, but much smaller than, findings with normal PSS. 3. For a given change in [Ca2+]i induced by ethanol, the developed tension was greater than that observed during contractions induced by high [K+]o. Thus, the [Ca2+]-tension curve for ethanol was shifted to the left of that for high [K+]o. The [Ca2+]-tension curve for the contraction induced by ethanol in the absence of extracellular Ca2+ was shifted further to the left from that obtained in the presence of [Ca2+]o. 4. The mechanisms involved in this Ca(2+)-sensitizing effect of ethanol were investigated using alpha-toxin-permeabilized coronary medial strips. Ethanol increased the tension development, in a concentration-dependent manner, at a fixed concentration of Ca2+ (pCa = 6.3) in the presence of guanosine-5'-triphosphate (GTP), an effect antagonized by guanosine-5'-O-(beta-thiodiphosphate) (GDP beta S), a non-hydrolysable GDP analogue. 5. With intact endothelium, the ethanol-induced tension development was markedly reduced, although inhibition in the increase in [Ca2+]i was slight. The [Ca2+]-tension relationship of this contraction overlapped with that obtained with high [K+]o-induced contraction and was shifted to the right from that obtained in the absence of the endothelium. This endothelium-dependent reduction of [Ca2+]i and tension induced by ethanol was inhibited when the strips were exposed to NG-monomethyl-L-arginine (L-NMMA). 6. Ethanol induced a gradual and sustained increase in [Ca2+]i in normal PSS, and a transient, concentration-dependent increase in [Ca2+]i in Ca(2+)-free PSS in porcine aortic valvular endothelial cells in situ.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of GTP-protein and endothelium in contraction induced by ethanol in pig coronary artery. 830 41

1. Mechanisms of Ca2+ sensitization of force production by noradrenaline were investigated by measuring contractile responses, intracellular Ca2+ concentration ([Ca2+]i) and phosphorylation of the myosin light chain (MLC) in intact and alpha-toxin-permeabilized rat mesenteric small arteries. 2. The effects of noradrenaline were investigated at constant membrane potential by comparing fully depolarized intact arteries in the absence and presence of noradrenaline. Contractile responses to K-PSS (125 mM K+) and NA-K-PSS (K-PSS + 10 microM noradrenaline) were titrated to 30 and 75%, respectively, of control force, by adjusting extracellular Ca2+ ([Ca2+]o). At both force levels, [Ca2+]i was substantially lower with NA-K-PSS than with K-PSS. With K-PSS, the proportion of MLC phosphorylated (approximately 30%) was similar at 30 and 75% of control force; with NA-K-PSS, MLC phosphorylation was greater at the higher force level (40 vs. 34%). 3. In alpha-toxin-permeabilized arteries, the force response to 1 microM Ca2+ was increased by 10 microM noradrenaline, and MLC phosphorylation was increased from 35 to 45%. The protein kinase C (PKC) inhibitor calphostin C (100 nM) abolished the noradrenaline-induced increase in MLC phosphorylation and contractile response, without affecting the contraction in response to Ca2+. Treatment with ATP gamma S in the presence of the MLC kinase inhibitor ML-9 increased the sensitivity to Ca2+ and abolished the response to noradrenaline. 4. The present results show that that in rat mesenteric small arteries noradrenaline-induced Ca2+ sensitization is associated with an increased proportion of phosphorylated MLC. The results are consistent with a decreased MLC phosphatase activity mediated through PKC. Furthermore, while MLC phosphorylation is a requirement for force production, the results show that other factors are also involved in force regulation.
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PMID:Mechanisms of Ca2+ sensitization of force production by noradrenaline in rat mesenteric small arteries. 970 5

1. This study was designed to investigate the mechanisms for the contractions induced by tachykinins (substance P (SP), neurokinin A (NKA) and neurokinin B (NKB)) in the rabbit corpus cavernosum strips, using fura-PE3 fluorimetry and alpha-toxin permeabilization. 2. Tachykinins induced contractions in the rabbit corpus cavernosum in a concentration-dependent manner. The potency order was SP>NKA>NKB. 3. The tachykinin-induced contractions were enhanced by phosphoramidon (PPAD), an endopeptidase inhibitor, but not by N(omega)-nitro-L-arginine methylester (L-NAME). 4. The NK(1) receptor selective antagonist, SR 140333 significantly inhibited the tachykinin-induced contractions. Although the NK(2) receptor selective antagonist, SR 48968 alone did not influence the effects of tachykinins, it potentiated the inhibitory effect of SR 140333. The NK(3) receptor selective antagonist, SR142801 had no effect. 5. In the rabbit corpus cavernosum, tachykinins induced sustained increases in [Ca(2+)](i) and tension in normal PSS, while only small transient increases in [Ca(2+)](i) and tension were observed in Ca(2+)-free solution. 6. In alpha-toxin permeabilized preparations, tachykinins induced an additional force development at a constant [Ca(2+)](i). 7. These results indicated that in the rabbit corpus cavernosum: (1) Tachykinins induced contractions by increasing both the [Ca(2+)](i) and myofilament Ca(2+) sensitivity; (2) The tachykinin-induced [Ca(2+)](i) elevations were mainly due to the Ca(2+) influx; (3) Tachykinin-induced contractions were mainly mediated through the activation of NK(1) receptor expressed in the rabbit corpus cavernosum smooth muscle, and affected by the endopeptidase activity and (4) Tachykinins may thus play a role in controlling the corpus cavernosum tone.
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PMID:The mechanisms for tachykinin-induced contractions of the rabbit corpus cavernosum. 1241 16