Caffeic Acid Esters Activate TREK-1 Potassium Channels and Inhibit Depolarization-Dependent Secretion

Danthi, Sanjay; Enyeart, Judith A.; Enyeart, John J.

doi:10.1124/mol.65.3.599

Cited by 27 publications

(39 citation statements)

References 35 publications

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“…Its increase in the probability of channel openings may primarily involve a decrease in the mean closed time [45]. This compound thus increases channel activity in a mechanism unlikely to be linked to its inhibition of activation of NF-κB [44,45]. By using the Ca 2+ -sensitive fluorescent dye fura-2, we also found out that CAPE could significantly reduce the firing and amplitude of intracellular Ca 2+ oscillations in pituitary GH 3 cells (Fig (2)).…”

Section: Cpae and Cdcmentioning

confidence: 86%

“…A recent report demonstrated that CAPE could protect the spinal cord and brain from ischemic injury [43]. Furthermore, CAPE and other structurally related compounds might activate background TREK-1 K + channels and inhibit depolarization-dependent secretion in bovine adrenal fasciculata cells [44]. TREK K + channels belong to the recently discovered superfamily of K + channels that contain two pore domains and four transmembrane segments.…”

Section: Cpae and Cdcmentioning

confidence: 99%

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Pharmacological Roles of the Large-Conductance Calcium-Activated Potassium Channel

Wu¹,

Wu²,

Lin³

2006

CTMC

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The gating of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel is primarily controlled by intracellular Ca(2+) and/or membrane depolarization. These channels play a role in the coupling of excitation-contraction and stimulus-secretion. A variety of structurally distinct compounds may influence the activity of these channels. Squamocin, an Annonaceous acetogenin, could interact with the BK(Ca) channel to increase the amplitude of Ca(2+)-activated K(+) current in coronary smooth muscle cells. Its stimulatory effect is related to intracellular Ca(2+) concentrations. In inside-out patches, application of ceramide to the bath suppressed the activity of BK(Ca) channels recorded from pituitary GH(3) cells and from retinal pigment epithelial cells. ICI-182,780, an estrogen receptor antagonist, was found to modulate BK(Ca)-channel activity in cultured endothelial cells and smooth muscle cells in a mechanism unlinked to the inhibition of estrogen receptors. Caffeic acid phenethyl ester (CAPE) and its analogy, cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate, could directly increase the activity of BK(Ca) channels in GH(3) cells. CAPE also reduced the frequency and amplitude of intracellular Ca(2+) oscillations in these cells. The CAPE-stimulated activity in BK(Ca) channels is thought to be unassociated with its inhibition of NF-kappaB activation. Cilostazol, an inhibitor of cyclic nucleotide phosphodiesterase, could stimulate BK(Ca) channel-activity and reduce the firing of action currents simultaneously in GH(3) cells. Therefore, the regulation by these compounds of BK(Ca) channels may in part be responsible for their regulatory actions on cell functions.

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Section: Cpae and Cdcmentioning

confidence: 86%

Section: Cpae and Cdcmentioning

confidence: 99%

Pharmacological Roles of the Large-Conductance Calcium-Activated Potassium Channel

Wu¹,

Wu²,

Lin³

2006

CTMC

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“…It has been suggested that caffeic acid derivatives bind to an external site to produce their effects on TREK1 channels, since activity was retained when the compounds were applied externally in outside-out patch recordings [24]. Recently, a range of substituted caffeic acid esters based on a hybrid of CDC and CAPE have been developed, the most promising of which (compound 12U) both enhances the activity of TREK1 channels and displays potent analgesic activity in vivo [84].…”

Section: Caffeic Acid Estersmentioning

confidence: 99%

Two-pore domain potassium channels: potential therapeutic targets for the treatment of pain

Mathie

Veale

2014

Pflugers Arch - Eur J Physiol

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Recent evidence points to a pivotal contribution of a variety of different potassium channels, including two-pore domain potassium (K2P) channels, in chronic pain processing. Expression of several different K2P channel subunits has been detected in nociceptive dorsal root ganglion neurons and trigeminal ganglion neurons, in particular, TREK1, TREK2, TRESK, TRAAK, TASK3 and TWIK1 channels. Of these, the strongest body of evidence from functional studies highlights the importance of TREK1, TRESK and, recently, TREK2 channels. For example, TREK1 knockout mice are more sensitive than wild-type mice to a number of painful stimuli but less sensitive to morphine-induced analgesia. TRESK knockdown mice show behavioural evidence of increased pain and increased sensitivity to painful pressure. Importantly, familial migraine with aura is associated with a dominant-negative mutation in human TRESK channels. Thus, the functional up-regulation of K2P channel activity may be a useful strategy in the development of new therapies for the treatment of pain. Whilst there are few currently available compounds that selectively and directly enhance the activity of TRESK and TREK2 channels, recent advances have been made in terms of identifying compounds that activate TREK1 channels and in understanding how they might act on the channel. Large-scale bio-informatic approaches and the further development of databases of putative ligands, channel structures and putative ligand binding sites on these structures may form the basis for future experimental strategies to detect novel molecules acting to enhance K2P channel activity that would be useful in the treatment of pain.

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“…Baicalein inhibits 12-lipoxygenase with an IC 50 of 0.015 M but does not activate bTREK-1 (8,13). At a concentration of 10 M, baicalein failed to inhibit ANG II-stimulated aldosterone secretion at either 1.5 or 16 h (Fig.…”

Section: Cdc Activates Btrek-1 Reverses Ang Ii-stimulated Membrane Dmentioning

confidence: 99%

TREK-1 K⁺channels couple angiotensin II receptors to membrane depolarization and aldosterone secretion in bovine adrenal glomerulosa cells

Enyeart

Danthi

Enyeart

2004

American Journal of Physiology-Endocrinology and Metabolism

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Bovine adrenal glomerulosa (AZG) cells were shown to express bTREK-1 background K+ channels that set the resting membrane potential and couple angiotensin II (ANG II) receptor activation to membrane depolarization and aldosterone secretion. Northern blot and in situ hybridization studies demonstrated that bTREK-1 mRNA is uniformly distributed in the bovine adrenal cortex, including zona fasciculata and zona glomerulosa, but is absent from the medulla. TASK-3 mRNA, which codes for the predominant background K+ channel in rat AZG cells, is undetectable in the bovine adrenal cortex. In whole cell voltage clamp recordings, bovine AZG cells express a rapidly inactivating voltage-gated K+ current and a noninactivating background K+ current with properties that collectively identify it as bTREK-1. The outwardly rectifying K+ current was activated by intracellular acidification, ATP, and superfusion of bTREK-1 openers, including arachidonic acid (AA) and cinnamyl 1–3,4-dihydroxy-α-cyanocinnamate (CDC). Bovine chromaffin cells did not express this current. In voltage and current clamp recordings, ANG II (10 nM) selectively inhibited the noninactivating K+ current by 82.1 ± 6.1% and depolarized AZG cells by 31.6 ± 2.3 mV. CDC and AA overwhelmed ANG II-mediated inhibition of bTREK-1 and restored the resting membrane potential to its control value even in the continued presence of ANG II. Vasopressin (50 nM), which also physiologically stimulates aldosterone secretion, inhibited the background K+ current by 73.8 ± 9.4%. In contrast to its potent inhibition of bTREK-1, ANG II failed to alter the T-type Ca2+ current measured over a wide range of test potentials by using pipette solutions of identical nucleotide and Ca2+-buffering compositions. ANG II also failed to alter the voltage dependence of T channel activation under these same conditions. Overall, these results identify bTREK-1 K+ channels as a pivotal control point where ANG II receptor activation is transduced to depolarization-dependent Ca2+ entry and aldosterone secretion.

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Caffeic Acid Esters Activate TREK-1 Potassium Channels and Inhibit Depolarization-Dependent Secretion

Abstract: In whole-cell and single-channel patch-clamp recordings from bovine adrenal fasciculata cells,

Cited by 27 publications

References 35 publications

Pharmacological Roles of the Large-Conductance Calcium-Activated Potassium Channel

Pharmacological Roles of the Large-Conductance Calcium-Activated Potassium Channel

Two-pore domain potassium channels: potential therapeutic targets for the treatment of pain

TREK-1 K⁺channels couple angiotensin II receptors to membrane depolarization and aldosterone secretion in bovine adrenal glomerulosa cells

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Caffeic Acid Esters Activate TREK-1 Potassium Channels and Inhibit Depolarization-Dependent Secretion

Abstract: In whole-cell and single-channel patch-clamp recordings from bovine adrenal fasciculata cells,

Cited by 27 publications

References 35 publications

Pharmacological Roles of the Large-Conductance Calcium-Activated Potassium Channel

Pharmacological Roles of the Large-Conductance Calcium-Activated Potassium Channel

Two-pore domain potassium channels: potential therapeutic targets for the treatment of pain

TREK-1 K+channels couple angiotensin II receptors to membrane depolarization and aldosterone secretion in bovine adrenal glomerulosa cells

Contact Info

Product

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TREK-1 K⁺channels couple angiotensin II receptors to membrane depolarization and aldosterone secretion in bovine adrenal glomerulosa cells