Expression-dependent pharmacology of transient receptor potential vanilloid subtype 1 channels in<i>Xenopus laevis</i>oocytes

Rivera-Acevedo, Ricardo E.; Pless, Stephan A.; Schwarz, Stephan; Ahern, Christopher A.

doi:10.4161/chan.23105

Cited by 6 publications

(3 citation statements)

References 35 publications

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“…This includes vertebrate homomeric glycine receptors [ 38 – 41 ], which are closely related members of the pLGIC family. In addition, such expression-dependent changes have been reported with structurally unrelated receptors, such as the ATP-gated P2X 2 receptor [ 42 ] and the transient receptor potential TRPV1 channel [ 43 ]. In these previously studies with homomeric receptors, it has been suggested that expression-dependent changes in apparent affinities may be a consequence of density-dependent changes in inter-receptor cooperativity or due to altered interactions with intracellular factors, both of which are likely to be associated with changes in receptor conformation [ 38 , 40 , 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Agonist and antagonist properties of an insect GABA-gated chloride channel (RDL) are influenced by heterologous expression conditions

et al. 2021

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Pentameric ligand-gated ion channels (pLGICs) activated by the inhibitory neurotransmitter γ-aminobutyric acid (GABA) are expressed widely in both vertebrate and invertebrate species. One of the best characterised insect GABA-gated chloride channels is RDL, an abbreviation of ‘resistance to dieldrin’, that was originally identified by genetic screening in Drosophila melanogaster. Here we have cloned the analogous gene from the bumblebee Bombus terrestris audax (BtRDL) and examined its pharmacological properties by functional expression in Xenopus oocytes. Somewhat unexpectedly, the sensitivity of BtRDL to GABA, as measured by its apparent affinity (EC50), was influenced by heterologous expression conditions. This phenomenon was observed in response to alterations in the amount of cRNA injected; the length of time that oocytes were incubated before functional analysis; and by the presence or absence of a 3’ untranslated region. In contrast, similar changes in expression conditions were not associated with changes in apparent affinity with RDL cloned from D. melanogaster (DmRDL). Changes in apparent affinity with BtRDL were also observed following co-expression of a chaperone protein (NACHO). Similar changes in apparent affinity were observed with an allosteric agonist (propofol) and a non-competitive antagonist (picrotoxinin), indicating that expression-depended changes are not restricted to the orthosteric agonist binding site. Interestingly, instances of expression-dependent changes in apparent affinity have been reported previously for vertebrate glycine receptors, which are also members of the pLGIC super-family. Our observations with BtRDL are consistent with previous data obtained with vertebrate glycine receptors and indicates that agonist and antagonist apparent affinity can be influenced by the level of functional expression in a variety of pLGICs.

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Section: Discussionmentioning

confidence: 99%

Agonist and antagonist properties of an insect GABA-gated chloride channel (RDL) are influenced by heterologous expression conditions

et al. 2021

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“…58 Surprisingly, QX-314 can exert biphasic effects on TRPV1 channels, which activate TRPV1 channels at higher (mM) concentrations and inhibit capsaicin-induced TRPV1 currents at lower (μM) concentrations. 51,59 However, nerve block is always established at a higher (mM) concentration, at which TRPV1 is also activated. TRPV1 is mainly expressed in unmyelinated afferent nerve fibers (small-diameter C-fiber), which is also the main target for the action of QLDs.…”

Section: Mechanism Of Action Of Qldsmentioning

confidence: 99%

Quaternary Lidocaine Derivatives: Past, Present, and Future

Wang¹,

Zhang²,

Liu³

et al. 2021

DDDT

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Local anesthetics have the advantage of complete analgesia with fewer side effects compared to systemic analgesics. However, their clinical use is limited due to their short duration of action. Thus, local anesthetics with fast onset, long duration of action, selective nociceptive block, and low local and systemic toxicity are highly desirable. In the past electrophysiological studies, quaternary lidocaine derivatives (QLDs) showed these characteristics. Here, we review electrophysiological properties of QLDs and their pharmacodynamic characteristics to shed light on potential problems.

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“…Notably, the TTX-7 enzyme is expressed in ASH neurons ( Tanizawa et al, 2006 ). Although the mammalian TRPV1 native membrane environment might be different from that of ASH neurons, TRPV1 features similar functional properties (e.g., polymodal activation and modulation) when measured in cells or systems with different lipidic composition (e.g., cultured dorsal root ganglia neurons, human embryonic kidney (HEK293) cells, Xenopus oocytes, insect cells, soybean lipids, or synthetic liposomes; Caterina et al, 1997 ; Nieto-Posadas et al, 2011 ; Rivera-Acevedo et al, 2013 ; Cao et al, 2013b ; Jara-Oseguera et al, 2016 ). Based on this knowledge, we sought to gain insight into TRPV1 regulation by phosphoinositide lipids by genetically manipulating their content in worms.…”

Section: Introductionmentioning

confidence: 99%

Deficiency of Inositol Monophosphatase Activity Decreases Phosphoinositide Lipids and Enhances TRPV1 FunctionIn Vivo

et al. 2020

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Membrane remodeling by inflammatory mediators influences the function of sensory ion channels. The capsaicin-and heat-activated TRPV1 channel contributes to neurogenic inflammation and pain hypersensitivity, in part due to its potentiation downstream of phospholipase C-coupled receptors that regulate phosphoinositide lipid content. Here, we determined the effect of phosphoinositide lipids on TRPV1 function by combining genetic dissection, diet supplementation, behavioral, biochemical, and functional analyses in Caenorhabditis elegans. As capsaicin elicits hot and pain sensation in mammals, transgenic TRPV1 worms exhibit an aversive response to capsaicin. TRPV1 worms with low levels of phosphoinositide lipids display an enhanced response to capsaicin, whereas phosphoinositide lipid supplementation reduces TRPV1-mediated responses. A worm carrying a TRPV1 construct lacking the distal C-terminal domain features an enhanced response to capsaicin, independent of the phosphoinositide lipid content. Our results demonstrate that TRPV1 activity is enhanced when the phosphoinositide lipid content is reduced, and the C-terminal domain is key to determining agonist response in vivo. 2 Significance Statement TRPV1 is an essential protein for the mechanism whereby noxious stimuli, such as high temperatures and chemicals, cause pain. TRPV1 undergoes sensitization, a process in which inflammatory molecules enhance its response to other stimuli, thereby promoting pain hypersensitivity. Proalgesic agents produced in response to tissue injury activate PLC-coupled receptors and alter the membrane phosphoinositide lipid content. The mechanism by which phosphoinositide lipids modulate TRPV1 function has remained controversial. Determining whether membrane phosphoinositides are positive or negative regulators of TRPV1 function is critical for developing therapeutic strategies to ameliorate TRPV1-mediated inflammatory pain. We address the role of phosphoinositide lipids on TRPV1 function using an in vivo approach and report that phosphoinositide lipids reduce TRPV1 activity in vivo.

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Expression-dependent pharmacology of transient receptor potential vanilloid subtype 1 channels inXenopus laevisoocytes

Cited by 6 publications

References 35 publications

Agonist and antagonist properties of an insect GABA-gated chloride channel (RDL) are influenced by heterologous expression conditions

Agonist and antagonist properties of an insect GABA-gated chloride channel (RDL) are influenced by heterologous expression conditions

Quaternary Lidocaine Derivatives: Past, Present, and Future

Deficiency of Inositol Monophosphatase Activity Decreases Phosphoinositide Lipids and Enhances TRPV1 FunctionIn Vivo

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