Different vanilloid agonists cause different patterns of calcium response in CHO cells heterologously expressing rat TRPV1

Tóth, Attila; Wang, Yun; Kedei, Noémi; Tran, Richard; Pearce, Larry V.; Kang, Sang-Uk; Jin, Mi-Kyung; Choi, Ho Jin; Lee, Jeeyeon; Blumberg, Peter M.

doi:10.1016/j.lfs.2004.10.056

Cited by 44 publications

(38 citation statements)

References 43 publications

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“…As can be seen, low concentrations of DA-5018 caused a gradually increasing level of intracellular calcium, similar to the pattern of response described for resiniferatoxin Toth et al, 2005). At higher concentrations of DA-5018, intracellular calcium reached a plateau, showing little subsequent decrease over the 15 min time course of the experiment.…”

Section: Resultssupporting

confidence: 79%

Differential modulation of agonist and antagonist structure activity relations for rat TRPV1 by cyclosporin A and other protein phosphatase inhibitors

Pearce

Tóth

Ryu

et al. 2008

Naunyn-Schmied Arch Pharmacol

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The transient receptor potential V1 channel (vanilloid receptor, TRPV1) represents a promising therapeutic target for inflammatory pain and other conditions involving C-fiber sensory afferent neurons. Sensitivity of TRPV1 is known to be subject to modulation by numerous signaling pathways, in particular by phosphorylation, and we wished to determine whether TRPV1 structure-activity relations could be differentially affected. We demonstrate here that the structure activity relations of TRPV1, as determined by 45 Ca 2+ uptake, were substantially altered by treatment of the cells with cyclosporin A, an inhibitor of protein phosphatase 2B. Whereas the potency of resiniferatoxin for stimulation of 45 Ca 2+ was not altered by cyclosporin A treatment, the potencies of some other agonists were increased up to 8-fold. Among antagonists examined, potencies were reduced to a lesser extent, ranging from 1-2.5 fold. Finally, the efficacy of partial agonists was increased. In contrast to cyclosporin A, okadaic acid, an inhibitor of protein phosphatases 1 and 2A, had little effect on agonist potencies, and calyculin A, an inhibitor of protein phosphatases 1 and 2A but with somewhat different selectivity from that of okadaic acid, caused changes in structure activity relations distinct from those induced by cyclosporin A. Because phosphatase activity differentially modulates the structure activity relations of TRPV1 agonists and antagonists, our findings predict that it may be possible to design agonist and antagonists selective for TRPV1 in a specific regulatory environment. A further implication is that it may be desirable to tailor screening approaches for drug discovery to reflect the desired regulatory state of the targeted TRPV1.

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Section: Resultssupporting

confidence: 79%

Differential modulation of agonist and antagonist structure activity relations for rat TRPV1 by cyclosporin A and other protein phosphatase inhibitors

Pearce

Tóth

Ryu

et al. 2008

Naunyn-Schmied Arch Pharmacol

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“…Columns represent mean Ϯ SEM (n = 5), significant differences (P < 0.05) from the control (wipes upon administration of the vehicle alone) are represented by asterisks. et al, 2003) 95 Ϯ 8 nM (Pearce et al, 2008) 35 Ϯ 11 nM (Toth et al, 2005b) Toth et al, 2005b) 221 nM 58 Ϯ 7%…”

Section: Figure 12mentioning

confidence: 98%

“…Resiniferatoxin 23 pM (Lee et al, 2001) 1.5 Ϯ 0.3 nM (Pearce et al, 2008) 81 Ϯ 20 pM (Toth et al, 2005b) -(Toth et al, 2005b No effect at 10 nM N/A + JYL-273 11 Ϯ 4 nM (Lee et al, 2001) 361 Ϯ 54 nM (Lee et al, 2002) No data…”

Section: + -mentioning

confidence: 99%

“…No data -195 No data 162 Ϯ 33 nM (Lee et al, 2002) 52 Ϯ 12 nM (Toth et al, 2005b) -(Toth et al, 2005b (Lee et al, 2001) 58 Ϯ 8 nM (Lee et al, 2002) 2.4 Ϯ 1.0 nM (Toth et al, 2005b) -(Toth et al, 2005b 3.9 nM 36 Ϯ 8% + + JYL-1511 50 Ϯ 17 nM (Wang et al, 2003) 3.4 Ϯ 0.5 mM (Wang et al, 2003) No data Wang et al, 2003) …”

Section: + -mentioning

confidence: 99%

“…Here we attempted to characterize this receptor pharmacologically. To achieve this, we chose a series of commercially available TRPV1 agonists and tested them in assays that measured not only their potency and efficacy, but also their kinetics of action and ability to induce desensitization (Toth et al, 2005b). Our experiments revealed different pharmacological profiles for vascular TRPV1 when compared with that of TRPV1 responsible for sensory activation.…”

Section: Introductionmentioning

confidence: 99%

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Structure‐activity relationships of vanilloid receptor agonists for arteriolar TRPV1

Czikora¹,

Lizanecz²,

Bakó³

et al. 2012

British J Pharmacology

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BACKGROUND AND PURPOSE The transient receptor potential vanilloid 1 (TRPV1) plays a role in the activation of sensory neurons by various painful stimuli and is a therapeutic target. However, functional TRPV1 that affect microvascular diameter are also expressed in peripheral arteries and we attempted to characterize this receptor. EXPERIMENTAL APPROACH Sensory TRPV1 activation was measured in rats by use of an eye wiping assay. Arteriolar TRPV1‐mediated smooth muscle specific responses (arteriolar diameter, changes in intracellular Ca2+) were determined in isolated, pressurized skeletal muscle arterioles obtained from the rat and wild‐type or TRPV1−/− mice and in canine isolated smooth muscle cells. The vascular pharmacology of the TRPV1 agonists (potency, efficacy, kinetics of action and receptor desensitization) was determined in rat isolated skeletal muscle arteries. KEY RESULTS Capsaicin evoked a constrictor response in isolated arteries similar to that mediated by noradrenaline, this was absent in arteries from TRPV1 knockout mice and competitively inhibited by TRPV1 antagonist AMG9810. Capsaicin increased intracellular Ca2+ in the arteriolar wall and in isolated smooth muscle cells. The TRPV1 agonists evoked similar vascular constrictions (MSK‐195 and JYL‐79) or were without effect (resiniferatoxin and JYL‐273), although all increased the number of responses (sensory activation) in the eye wiping assay. Maximal doses of all agonists induced complete desensitization (tachyphylaxis) of arteriolar TRPV1 (with the exception of capsaicin). Responses to the partial agonist JYL‐1511 suggested 10% TRPV1 activation is sufficient to evoke vascular tachyphylaxis without sensory activation. CONCLUSIONS AND IMPLICATIONS Arteriolar TRPV1 have different pharmacological properties from those located on sensory neurons in the rat.

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Capsaicinoids: Occurrence, Chemistry, Biosynthesis, and Biological Effects

Kaiser

Higuera

Goycoolea

2017

Fruit and Vegetable Phytochemicals

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Different vanilloid agonists cause different patterns of calcium response in CHO cells heterologously expressing rat TRPV1

Cited by 44 publications

References 43 publications

Differential modulation of agonist and antagonist structure activity relations for rat TRPV1 by cyclosporin A and other protein phosphatase inhibitors

Differential modulation of agonist and antagonist structure activity relations for rat TRPV1 by cyclosporin A and other protein phosphatase inhibitors

Structure‐activity relationships of vanilloid receptor agonists for arteriolar TRPV1

Capsaicinoids: Occurrence, Chemistry, Biosynthesis, and Biological Effects

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