The Calcium Channel Blocker Gabapentin, a Benchmark Drug in Pain Studies, Inhibits Translocation of the Epsilon Isoform of Protein Kinase C in Cultured Nociceptors: A Novel Mechanism of Action

2021 ◽  
pp. 47-56
Author(s):  
Vittorio Vellani ◽  
Chiara Giacomoni
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Mechanism Of Action ◽  
Channel Blocker ◽  
Kinase C

Chronic treatment by the calcium channel blocker ± PN 200-110 in the rat counteracts the stimulations of pituitary weight, prolactin release and pituitary C-kinase activity induced by a chronic estradiol treatment, in vivo

1990 ◽  
Vol 122 (3) ◽  
pp. 403-408
Author(s):  
Ph. Touraine ◽  
P. Birman ◽  
F. Bai-Grenier ◽  
C. Dubray ◽  
F. Peillon ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Plasma Prolactin ◽  
Estradiol Treatment ◽  
Kinase C ◽  
Protein Kinase C Activity

Abstract In order to investigate whether a calcium channel blocker could modulate the protein kinase C activity in normal and estradiol pretreated rat pituitary, female Wistar rats were treated or not (controls) with ± PN 200-110 (3 mg · kg−1 · day−1, sc) for 8 days or with estradiol cervical implants for 8 or 15 days, alone or in combination with PN 200-110 the last 8 days. Estradiol treatment induced a significant increase in plasma prolactin levels and pituitary weight. PN 200-110 administered to normal rats did not modify these parameters, whereas it reduced the effects of the 15 days estradiol treatment on prolactin levels (53.1 ± 4.9 vs 95.0 ±9.1 μg/l, p<0.0001) and pituitary weight (19.9 ± 0.4 vs 23.0 ± 0.6 mg, p <0.001), to values statistically comparable to those measured after 8 days of estradiol treatment. PN 200-110 alone did not induce any change in protein kinase C activity as compared with controls. In contrast, PN 200-110 treatment significantly counteracted the large increase in soluble activity and the decrease in the particulate one induced by estradiol between day 8 and day 15. We conclude that PN 200-110 opposed the stimulatory effects of chronic in vivo estradiol treatment on plasma prolactin levels and pituitary weight and that this regulation was related to a concomitant modulation of the protein kinase C activity.

Role of calcium channels and protein kinase C for release of norepinephrine and neuropeptide Y

1990 ◽  
Vol 259 (5) ◽  
pp. R925-R930
Author(s):  
M. Haass ◽  
C. Forster ◽  
G. Richardt ◽  
R. Kranzhofer ◽  
A. Schomig
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Neuropeptide Y ◽  
Nerve Fibers ◽  
Extracellular Calcium ◽  
Minor Effect ◽  
Kinase C

The role of calcium for the release of norepinephrine (NE, determined by high-pressure liquid chromatography) and neuropeptide Y (NPY, determined by radioimmunoassay) was investigated in guinea pig perfused hearts with intact sympathetic innervation. In the presence of extracellular calcium (1.85 mM), electrical stimulation of the left stellate ganglion (12 Hz, 1 min) induced a closely related release of NE and NPY with the molar ratio of approximately 400-600 (NE) to 1 (NPY). The stimulation-evoked overflow of both transmitters was dependent from the extracellular calcium concentration and was almost completely suppressed by calcium-free perfusion. The corelease of both transmitters was not affected by the L-type calcium channel blocker felodipine (1-10 microM). However, the overflow of NE and NPY was markedly attenuated by the unselective calcium antagonist flunarizine (1-10 microM) and completely prevented by the neuronal (N-type) calcium channel blockers omega-conotoxin (1-100 nM) and cadmium chloride (10-100 microM), indicating a key role for N-type calcium channels in the exocytotic release of transmitters from cardiac sympathetic nerve fibers. Possibly due to unspecific actions, such as interference with sodium channels or uptake1-blocking properties, the phenylalkylamines verapamil (0.01-10 microM) and gallopamil (1-10 microM) reduced NPY overflow with only a minor effect on NE overflow. The stimulation-induced transmitter release was increased up to twofold by activation of protein kinase C (phorbol 12-myristate 13-acetate, 3 nM-3 microM) and completely suppressed by inhibition of protein kinase C (polymyxin B, 100 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Potassium channels modulate canine pulmonary vasoreactivity to protein kinase C activation

1999 ◽  
Vol 277 (3) ◽  
pp. L558-L565 ◽  
Author(s):  
Scott A. Barman
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Channel Blocker ◽  
Pressor Response ◽  
Vascular Occlusion ◽  
Membrane Depolarization ◽  
Delayed Rectifier ◽  
Vascular Compliance ◽  
Kinase C ◽  
Pkc Activation

The role of Ca2+-activated K+-channel, ATP-sensitive K+-channel, and delayed rectifier K+-channel modulation in the canine pulmonary vascular response to protein kinase C (PKC) activation was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. The PKC activators phorbol 12-myristate 13-acetate (PMA; 10−7 M) and thymeleatoxin (THX; 10−7 M) significantly increased pulmonary arterial and pulmonary venous resistances and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. The Ca2+-activated K+-channel blocker tetraethylammonium ions (1 mM), the ATP-sensitive K+-channel inhibitor glibenclamide (10−5 M), and the delayed rectifier K+-channel blocker 4-aminopyridine (10−4 M) potentiated the pressor response to both PMA and THX on the arterial and venous segments and also further decreased pulmonary vascular compliance. In contrast, the ATP-sensitive K+-channel opener cromakalim (10−5 M) attenuated the vasoconstrictor effect of PMA and THX on both the arterial and venous vessels. In addition, membrane depolarization by 30 mM KCl elicited an increase in the pressor response to PMA. These results indicate that pharmacological activation of PKC elicits pulmonary vasoconstriction. Closure of the Ca2+-activated K+ channels, ATP-sensitive K+ channels, and delayed rectifier K+ channels as well as direct membrane depolarization by KCl potentiated the response to PMA and THX, indicating that K+ channels modulate the canine pulmonary vasoconstrictor response to PKC activation.

scholarly journals Role of protein kinase C in Ca channel blocker-induced renal arteriolar dilation in spontaneously hypertensive rats

2005 ◽  
Vol 54 (2) ◽  
pp. 102-108 ◽  
Author(s):  
Koichi Hayashi ◽  
Shu Wakino ◽  
Yuri Ozawa ◽  
Koichiro Homma ◽  
Takeshi Kanda ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Spontaneously Hypertensive Rats ◽  
Channel Blocker ◽  
Ca Channel ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Kinase C

Mechanism of action of growth hormone in adipocytes: a role for protein kinase C?

1993 ◽  
Vol 21 (4) ◽  
pp. 376S-376S
Author(s):  
RICHARD G. VERNON ◽  
SYLVIA LINDSAY-WATT ◽  
ERIC FINLEY
Keyword(s):  
Growth Hormone ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Mechanism Of Action ◽  
Kinase C

Overexpression of RHO Inhibitor and PAK as Possible Treatments For Restoring Sharp Features in Cancer Cells

2001 ◽  
Vol 7 (S2) ◽  
pp. 576-577
Author(s):  
Heckman C. A. ◽  
Urban J. M. ◽  
Wales T. S. ◽  
Cayer M. L. ◽  
Barnes J. A. ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Mechanism Of Action ◽  
Tumor Promoter ◽  
Shape Features ◽  
Cell Edge ◽  
Kinase C ◽  
Bona Fide ◽  
Rho Family

The mechanism of action of the tumor promoter, phorbol 12-myristate 13-acetate (PMA), depends on its ability to substitute for an endogenous second messenger, diacylglycerol, and thereby activate certain members of an enzyme family known as protein kinase C. Previous work from this laboratory showed that the quantitative shape phenotype of cells treated with PMA resembled the phenotype of bona fidecancer cells. The effect of PMA on this phenotype was transient, and was restricted to a period of two- to five-hours after exposure to PMA. When the shape phenotype was dissected into components by relating different variable's values to shape features, several of the altered values appeared to rely upon a declining number of sharp features, such as filopodia and microspikes, at the cell edge.Filopodia and microspikes are in turn regulated by a GTPase of the Rho family, Cdc42, which modulates actin architecture.

scholarly journals Macrocyclic Diterpenoids from Euphorbiaceae as A Source of Potent and Selective Inhibitors of Chikungunya Virus Replication

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2336 ◽  
Author(s):  
Simon Remy ◽  
Marc Litaudon
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Virus Replication ◽  
Mechanism Of Action ◽  
Chikungunya Virus ◽  
Cytopathic Effect ◽  
Structural Diversity ◽  
Biological Properties ◽  
Kinase C ◽  
Structure Activity

Macrocyclic diterpenoids produced by plants of the Euphorbiaceae family are of considerable interest due to their high structural diversity; and their therapeutically relevant biological properties. Over the last decade many studies have reported the ability of macrocyclic diterpenoids to inhibit in cellulo the cytopathic effect induced by the chikungunya virus. This review; which covers the years 2011 to 2019; lists all macrocyclic diterpenoids that have been evaluated for their ability to inhibit viral replication. The structure–activity relationships and the probable involvement of protein kinase C in their mechanism of action are also detailed.

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