Ruthenium red as a capsaicin antagonist

Amann, Rainer; Maggi, Carlo Alberto

doi:10.1016/0024-3205(91)90169-c

Cited by 145 publications

(68 citation statements)

References 45 publications

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“…Similar experiments were performed with the noncompetitive vanilloid receptor antagonist ruthenium red (Amann and Maggi, 1991). When applied together with RTX, ruthenium red blocked the 45 Ca uptake into the cells induced by 200 nM RTX in a dose-dependent fashion, with an ED 50 of 790 Ϯ 40 nM (mean Ϯ SEM for three determinations) (Fig.…”

Section: Resultssupporting

confidence: 55%

Differential Activation and Desensitization of Sensory Neurons by Resiniferatoxin

et al. 1997

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Recently, with use of rat dorsal root ganglion (DRG) neurons we have been able to dissociate the binding affinities of vanilloids from their potencies to induce 45 Ca uptake, which suggests the existence of distinct classes of the vanilloid receptor (Acs et al., 1996). In the present study, we have demonstrated that the ultrapotent capsaicin analog resiniferatoxin (RTX) desensitized rat DRG neurons to the subsequent induction of 45 Ca uptake by capsaicin and RTX with affinity and cooperativity similar to that found for [3 H]RTX binding, contrasting with a ϳ10-fold weaker potency and lack of cooperativity to induce 45 Ca uptake. Likewise, the competitive antagonist capsazepine inhibited RTXinduced desensitization with potency similar to that for inhibition of specific [ 3 H]RTX binding, whereas the potency of capsazepine was ϳ10-fold higher for inhibiting RTX-induced 45 Ca uptake. Finally, the noncompetitive antagonist ruthenium red inhibited both the RTX-induced desensitization and 45 Ca uptake but showed ϳ60-fold selectivity for inhibiting RTXinduced desensitization. The RTX-induced desensitization was not associated with loss of specific [3 H]RTX binding, suggesting lack of gross cell toxicity. In contrast to RTX, capsaicin caused desensitization with a potency corresponding to that for 45 Ca uptake and did so in a noncooperative manner. Unlike the RTX-induced desensitization, the desensitization by capsaicin was blocked by ruthenium red only at doses that blocked 45 Ca uptake and depended on external calcium. Our findings provide further support for the existence of vanilloid receptor subtypes on DRG neurons with distinct pharmacology and distinct patterns of desensitization.

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Section: Resultssupporting

confidence: 55%

Differential Activation and Desensitization of Sensory Neurons by Resiniferatoxin

et al. 1997

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“…In regard to the specificity of the inhibition of the VDAC and UP it is relevant that RuRed also inhibits plasma membrane and intracellular cation channels (e.g. TASK-3 [40], TRPV [41] and RyR [42], respectively). [20].…”

Section: (3) Inhibition Of the Mitochondrial Uptake Sitesmentioning

confidence: 99%

Mitochondrial calcium signalling and cell death: Approaches for assessing the role of mitochondrial Ca2+ uptake in apoptosis

et al. 2006

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SummaryLocal Ca 2+ transfer between adjoining domains of the sarcoendoplasmic reticulum (ER/SR) and mitochondria allows ER/SR Ca 2+ release to activate mitochondrial Ca 2+ uptake and to evoke a matrix [Ca 2+ ] ([Ca 2+ ] m ) rise. [Ca 2+ ] m exerts control on several steps of energy metabolism to synchronize ATP generation with cell function. However, calcium signal propagation to the mitochondria may also ignite a cell death program through opening of the permeability transition pore (PTP). This occurs when the Ca 2+ release from the ER/SR is enhanced or is coincident with sensitization of the PTP. Recent studies have shown that several pro-apoptotic factors, including members of the Bcl-2 family proteins and reactive oxygen species (ROS) regulate the Ca 2+ sensitivity of both the Ca 2+ release channels in the ER and the PTP in the mitochondria. To test the relevance of the mitochondrial Ca 2+ accumulation in various apoptotic paradigms, methods are available for buffering of [Ca 2+ ], for dissipation of the driving force of the mitochondrial Ca 2+ uptake and for inhibition of the mitochondrial Ca 2+ transport mechanisms. However, in intact cells, the efficacy and the specificity of these approaches have to be established. Here we discuss mechanisms that recruit the mitochondrial calcium signal to a pro-apoptotic cascade and the approaches available for assessment of the relevance of the mitochondrial Ca 2+ handling in apoptosis. We also present a systematic evaluation of the effect of ruthenium red and Ru360, two inhibitors of mitochondrial Ca 2+ uptake on cytosolic [Ca 2+ Mitochondrial Ca 2+ transport mechanismsThe pathways of the mitochondrial Ca 2+ import and export are illustrated in Fig1. Ca 2+ traverses the outer mitochondrial membrane (OMM) primarily through the voltage dependent anion-selective channel (VDAC) [1][2][3]. The molecular nature of the proteins mediating the Ca 2+ transport across the inner mitochondrial membrane (IMM) remains unknown. The protein mediating Ca 2+ uptake is referred as the uniporter (UP) and has been identified as a Ca 2+ selective ion channel [4]. The UP passes Ca 2+ along the electrochemical gradient largely due Correspondence to: Dr. György Hajnóczky, Department of Pathology, Anatomy and Cell Biology, Suite 261 JAH, Thomas Jefferson University, Philadelphia PA 19107, USA, Tel.: (215) 503-1427, Fax.: (215) 923-2218, E-mail: E-mail: Gyorgy.Hajnoczky@jefferson.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In the sequence from the opening of the IP3Rs to the opening of the PTP, the calcium signal propagation may be affec...

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“…It increased by about 1500% under a first stimulation with 1 µM capsaicin and about 150% after a second 1 µM capsaicin stimulation; under acid pH values of 6-7 CGRP outflow increased 250%. 5) On the basis of these figures, our experimental conditions, treatment of rat atria with 0.5 µM capsaicin and/or pH of about 6.7, should be appropriate stimuli for CGRP release from sensory nerve terminals. We have previously reported that 0.5 µM capsaicin increased contractility and relaxation in electrically paced rat atria and that 1 µM CGRP 8-37 effectively prevented these capsaicin effects.…”

Section: Discussionmentioning

confidence: 99%

“…5) However, it has been recently proposed that low pH could not be the endogenous activator of the cation channel stimulated by capsaicin in sensory neurons. 6) In the isolated guinea-pig heart, capsaicin, ischemia and acid pH evoke increases in the outflow of CGRP.…”

mentioning

confidence: 99%

Influence of Calcitonin Gene-related Peptide Release on pH-induced Mechanical Depression in Rat Atria.

Alvis

Milesi

Rebolledo³

et al. 2001

Jpn Heart J

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SUMMARYRat atria is richly innervated by sensory nerve fibers that release CGRP when stimulated either by capsaicin or acid pH. We studied the physiological relevance of acid pHinduced CGRP release on changes in atrial contractility and relaxation produced by lowering the pH. Isolated atria electrically paced at 2.77 Hz were exposed to a 10-minute period of metabolic acidosis (pH=6.73±0.01, n=28) after: 1) CGRP release induced by capsaicin 0.5 µM; 2) blockage of CGRP release with ruthenium red (RR) 5 µM; 3) no pretreatment; and 4) CGRP receptor blockage with CGRP 8-37 1 µM. Contractility and relaxation were significantly less depressed by acid pH when CGRP release was prevented by RR or CGRP receptor activation was blocked by CGRP . The results suggest that CGRP release and the activation of CGRP receptors may be physiologically involved in contributing to the depression of contractility and relaxation induced by acid pH in rat atria. (Jpn Heart J 2001; 42: 507-517)

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Ruthenium red as a capsaicin antagonist

Cited by 145 publications

References 45 publications

Differential Activation and Desensitization of Sensory Neurons by Resiniferatoxin

Differential Activation and Desensitization of Sensory Neurons by Resiniferatoxin

Mitochondrial calcium signalling and cell death: Approaches for assessing the role of mitochondrial Ca2+ uptake in apoptosis

Influence of Calcitonin Gene-related Peptide Release on pH-induced Mechanical Depression in Rat Atria.

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