Selective inhibition of the phospholipase C pathway blocks one light-activated current component in Limulus photoreceptor

1995 ◽  
Vol 177 (5) ◽  
Author(s):  
K. Contzen ◽  
K.-H. Richter ◽  
K. Nagy
2003 ◽  
Vol 163 (5) ◽  
pp. 1157-1165 ◽  
Author(s):  
Elsa-Noah N'Diaye ◽  
Eric J. Brown

PLIC-1, a newly described ubiquitin-related protein, inhibited both Jurkat migration toward SDF-1α and A431 wound healing, but the closely related PLIC-2 did not. PLIC-1 prevented the SDF-1α–induced activation of phospholipase C, decreased ligand-induced internalization of SDF-1α receptor CXCR4 and inhibited chemotaxis signaled by a transfected Gi-coupled receptor. However, PLIC-1 had no effect on Gs-mediated adenylyl cyclase activation, and inhibited only the Gβγ-dependent component of Gq-initiated increase in [Ca2+]i, which is consistent with selective inhibition of Gβγ function. PLIC-1 colocalized with G proteins in lamellae and pseudopods, and precipitated Gβγ in pull downs. Interaction with Gβγ did not require PLIC-1's ubiquitin-like or ubiquitin-associated domains, and proteasome inhibition had no effect on SDF-1α activation of phospholipase C, indicating that PLIC-1's inhibition of Gβγ did not result from effects on proteasome function. Thus, PLIC-1 inhibits Gi signaling by direct association with Gβγ; because it also interacts with CD47, a modulator of integrin function, it likely has a role integrating adhesion and signaling components of cell migration.


1990 ◽  
Vol 68 (2) ◽  
pp. 520-527 ◽  
Author(s):  
V. G. Mahadevappa ◽  
Frank Sicilia

In the present work we investigated the effect of serine esterase inhibitors such as 2-nitro-4-carboxyphenyl N,N-diphenylcarbamate (NCDC) and phenylmethylsulfonyl fluoride (PMSF), as well as the effect of mepacrine on thrombin-induced mobilization of arachidonic acid (AA) in human platelets. The inhibitor NCDC (0.6 mM) completely abolished the thrombin-induced activation of phospholipase C, phospholipase A2, and transacylase enzymes, whereas the pretreatment of platelets with PMSF (2 mM) resulted in a highly selective inhibition of phospholipase A2 and transacylase activities, with no marked effect on thrombin-induced activation of phospholipase C. The thrombin-induced release of [3H]AA from phosphatidylcholine and phosphatidylinositol was reduced by 90 and 56%, respectively, in the presence of PMSF. This inhibitor also caused a parallel inhibition in the accumulation of [3H]AA (85%) with little effect on thrombin-induced formation of [3H]phosphatidic acid (5%), whereas mepacrine (0.4 mM) caused a selective inhibition of phospholipase A2 and transacylase activities with concomitant stimulation of [3H]phosphatidic acid formation in intact human platelets. These results demonstrate that NCDC and PMSF (serine esterase inhibitors) do not affect agonist-induced activation of phospholipases that mobilize arachidonic acid through a common site. Our results further demonstrate that the inhibition of [3H]AA release observed in the presence of NCDC, PMSF, and mepacrine is primarily due to their direct effects on enzyme activities, rather than due to their indirect effects through formation of complexes between inhibitors and membrane phospholipids. Based upon these results, we also conclude that the combined hydrolysis of phosphatidylcholine and phosphatidylinositol by phospholipase A2 serves as a major source for eicosanoid biosynthesis in thrombin-stimulated human platelets.Key words: deacylation, phospholipids, thrombin, platelets, phospholipase A2.


1997 ◽  
Vol 14 (5) ◽  
pp. 995-998 ◽  
Author(s):  
Károly Nagy ◽  
Klaus Contzen

AbstractIn the ventral nerve photoreceptor of Limulus a short, intense flash evokes a receptor current consisting of three components. In contrast to other hypotheses, we suggested previously that only the second component of the current is activated by the phospholipase C pathway, which releases calcium from intracellular stores by inositol trisphosphate. The present paper gives further evidence to our suggestion. It is demonstrated that U-73122, a specific inhibitor for the phospholipase C, selectively blocks the second component. The first and third components are moderately affected and could still be activated after the complete block of the second one. Results support the idea that the first and third components areactivated by pathways operating independently of phospholipase C.


2007 ◽  
Vol 74 ◽  
pp. 37-45 ◽  
Author(s):  
James W. Putney

The original hypothesis put forth by Bob Michell in his seminal 1975 review held that inositol lipid breakdown was involved in the activation of plasma membrane calcium channels or ‘gates’. Subsequently, it was demonstrated that while the interposition of inositol lipid breakdown upstream of calcium signalling was correct, it was predominantly the release of Ca2+ that was activated, through the formation of Ins(1,4,5)P3. Ca2+ entry across the plasma membrane involved a secondary mechanism signalled in an unknown manner by depletion of intracellular Ca2+ stores. In recent years, however, additional non-store-operated mechanisms for Ca2+ entry have emerged. In many instances, these pathways involve homologues of the Drosophila trp (transient receptor potential) gene. In mammalian systems there are seven members of the TRP superfamily, designated TRPC1–TRPC7, which appear to be reasonably close structural and functional homologues of Drosophila TRP. Although these channels can sometimes function as store-operated channels, in the majority of instances they function as channels more directly linked to phospholipase C activity. Three members of this family, TRPC3, 6 and 7, are activated by the phosphoinositide breakdown product, diacylglycerol. Two others, TRPC4 and 5, are also activated as a consequence of phospholipase C activity, although the precise substrate or product molecules involved are still unclear. Thus the TRPCs represent a family of ion channels that are directly activated by inositol lipid breakdown, confirming Bob Michell's original prediction 30 years ago.


2000 ◽  
Vol 111 (2) ◽  
pp. 432-440 ◽  
Author(s):  
Davide Gibellini ◽  
Alessandra Bassini ◽  
Maria Carla Re ◽  
Cristina Ponti ◽  
Sebastiano Miscia ◽  
...  

2018 ◽  
Vol 32 (4) ◽  
pp. 182-190 ◽  
Author(s):  
Kenta Matsumura ◽  
Koichi Shimizu ◽  
Peter Rolfe ◽  
Masanori Kakimoto ◽  
Takehiro Yamakoshi

Abstract. Pulse volume (PV) and its related measures, such as modified normalized pulse volume (mNPV), direct-current component (DC), and pulse rate (PR), derived from the finger-photoplethysmogram (FPPG), are useful psychophysiological measures. Although considerable uncertainties exist in finger-photoplethysmography, little is known about the extent of the adverse effects on the measures. In this study, we therefore examined the inter-method reliability of each index across sensor positions and light intensities, which are major disturbance factors of FPPG. From the tips of the index fingers of 12 participants in a resting state, three simultaneous FPPGs having overlapping optical paths were recorded, with their light intensity being changed in three steps. The analysis revealed that the minimum values of three coefficients of Cronbach’s α for ln PV, ln mNPV, ln DC, and PR across positions were .948, .850, .922, and 1.000, respectively, and that those across intensities were .774, .985, .485, and .998, respectively. These findings suggest that ln mNPV and PR can be used for psychophysiological studies irrespective of minor differences in sensor attachment positions and light source intensity, whereas and ln DC can also be used for such studies but under the condition of light intensity being fixed.


2018 ◽  
Vol 11 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Neil M. Drummond ◽  
Erin K. Cressman ◽  
Anthony N. Carlsen

Pneumologie ◽  
2013 ◽  
Vol 67 (05) ◽  
Author(s):  
D Kosanovic ◽  
BK Dahal ◽  
C Vroom ◽  
E Bieniek ◽  
H Ardeschir Ghofrani ◽  
...  

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