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Article: Acidosis antagonizes intracellular calcium response to κ-opioid receptor stimulation in the rat heart

TitleAcidosis antagonizes intracellular calcium response to κ-opioid receptor stimulation in the rat heart
Acidosis antagonizes intracellular calcium response to kappa-opioid receptor stimulation in the rat heart
Authors
Issue Date1999
PublisherAmerican Physiological Society. The Journal's web site is located at http://ajpcon.physiology.org/
Citation
American Journal of Physiology, 1999, v. 277 n. 3, p. C492-C500 How to Cite?
AbstractTo study the effects of kappa-opioid receptor stimulation on intracellular Ca2+ concentration ([Ca2+]i) homeostasis during extracellular acidosis, we determined the effects of kappa-opioid receptor stimulation on [Ca2+]i responses during extracellular acidosis in isolated single rat ventricular myocytes, by a spectrofluorometric method. U-50488H (10-30 microM), a selective kappa-opioid receptor agonist, dose dependently decreased the electrically induced [Ca2+]i transient, which results from the influx of Ca2+ and the subsequent mobilization of Ca2+ from the sarcoplasmic reticulum (SR). U-50488H (30 microM) also increased the resting [Ca2+]i and inhibited the [Ca2+]i transient induced by caffeine, which mobilizes Ca2+ from the SR, indicating that the effects of the kappa-opioid receptor agonist involved mobilization of Ca2+ from its intracellular pool into the cytoplasm. The Ca2+ responses to 30 microM U-50488H were abolished by 5 microM nor-binaltorphimine, a selective kappa-opioid receptor antagonist, indicating that the event was mediated by the kappa-opioid receptor. The effects of the agonist on [Ca2+]i and the electrically induced [Ca2+]i transient were significantly attenuated when the extracellular pH (pHe) was lowered to 6.8, which itself reduced intracellular pH (pHi) and increased [Ca2+]i. The inhibitory effects of U-50488H were restored during extracellular acidosis in the presence of 10 microM ethylisopropyl amiloride, a potent Na+/H+ exchange blocker, or 0.2 mM Ni2+, a putative Na+/Ca2+ exchange blocker. The observations indicate that acidosis may antagonize the effects of kappa-opioid receptor stimulation via Na+/H+ and Na+/Ca2+ exchanges. When glucose at 50 mM, known to activate the Na+/H+ exchange, was added, both the resting [Ca2+]i and pHi increased. Interestingly, the effects of U-50488H on [Ca2+]i and the electrically induced [Ca2+]i transient during superfusion with glucose were significantly attenuated; this mimicked the responses during extracellular acidosis. When a high-Ca2+ (3 mM) solution was superfused, the resting [Ca2+]i increased; the increase was abolished by 0.2 mM Ni2+, but the pHi remained unchanged. Like the responses to superfusion with high-concentration glucose and extracellular acidosis, the responses of the [Ca2+]i and electrically induced [Ca2+]i transients to 30 microM U-50488H were also significantly attenuated. Results from the present study demonstrated for the first time that extracellular acidosis antagonizes the effects of kappa-opioid receptor stimulation on the mobilization of Ca2+ from SR. Activation of both Na+/H+ and Na+/Ca2+ exchanges, leading to an elevation of [Ca2+]i, may be responsible for the antagonistic action of extracellular acidosis against kappa-opioid receptor stimulation.
Persistent Identifierhttp://hdl.handle.net/10722/210225
ISSN
1998 Impact Factor: 3.077
2004 SCImago Journal Rankings: 1.102

 

DC FieldValueLanguage
dc.contributor.authorPei, J-
dc.contributor.authorYu, X-
dc.contributor.authorBian, JS-
dc.contributor.authorWong, TM-
dc.date.accessioned2015-05-29T01:36:28Z-
dc.date.available2015-05-29T01:36:28Z-
dc.date.issued1999-
dc.identifier.citationAmerican Journal of Physiology, 1999, v. 277 n. 3, p. C492-C500-
dc.identifier.issn0002-9513-
dc.identifier.urihttp://hdl.handle.net/10722/210225-
dc.description.abstractTo study the effects of kappa-opioid receptor stimulation on intracellular Ca2+ concentration ([Ca2+]i) homeostasis during extracellular acidosis, we determined the effects of kappa-opioid receptor stimulation on [Ca2+]i responses during extracellular acidosis in isolated single rat ventricular myocytes, by a spectrofluorometric method. U-50488H (10-30 microM), a selective kappa-opioid receptor agonist, dose dependently decreased the electrically induced [Ca2+]i transient, which results from the influx of Ca2+ and the subsequent mobilization of Ca2+ from the sarcoplasmic reticulum (SR). U-50488H (30 microM) also increased the resting [Ca2+]i and inhibited the [Ca2+]i transient induced by caffeine, which mobilizes Ca2+ from the SR, indicating that the effects of the kappa-opioid receptor agonist involved mobilization of Ca2+ from its intracellular pool into the cytoplasm. The Ca2+ responses to 30 microM U-50488H were abolished by 5 microM nor-binaltorphimine, a selective kappa-opioid receptor antagonist, indicating that the event was mediated by the kappa-opioid receptor. The effects of the agonist on [Ca2+]i and the electrically induced [Ca2+]i transient were significantly attenuated when the extracellular pH (pHe) was lowered to 6.8, which itself reduced intracellular pH (pHi) and increased [Ca2+]i. The inhibitory effects of U-50488H were restored during extracellular acidosis in the presence of 10 microM ethylisopropyl amiloride, a potent Na+/H+ exchange blocker, or 0.2 mM Ni2+, a putative Na+/Ca2+ exchange blocker. The observations indicate that acidosis may antagonize the effects of kappa-opioid receptor stimulation via Na+/H+ and Na+/Ca2+ exchanges. When glucose at 50 mM, known to activate the Na+/H+ exchange, was added, both the resting [Ca2+]i and pHi increased. Interestingly, the effects of U-50488H on [Ca2+]i and the electrically induced [Ca2+]i transient during superfusion with glucose were significantly attenuated; this mimicked the responses during extracellular acidosis. When a high-Ca2+ (3 mM) solution was superfused, the resting [Ca2+]i increased; the increase was abolished by 0.2 mM Ni2+, but the pHi remained unchanged. Like the responses to superfusion with high-concentration glucose and extracellular acidosis, the responses of the [Ca2+]i and electrically induced [Ca2+]i transients to 30 microM U-50488H were also significantly attenuated. Results from the present study demonstrated for the first time that extracellular acidosis antagonizes the effects of kappa-opioid receptor stimulation on the mobilization of Ca2+ from SR. Activation of both Na+/H+ and Na+/Ca2+ exchanges, leading to an elevation of [Ca2+]i, may be responsible for the antagonistic action of extracellular acidosis against kappa-opioid receptor stimulation.-
dc.languageeng-
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://ajpcon.physiology.org/-
dc.relation.ispartofAmerican Journal of Physiology-
dc.rightsAmerican Journal of Physiology. Copyright © American Physiological Society.-
dc.rightsThis is an unofficial adaptation or translation of an article that appeared in a publication of the American Physiological Society. The American Physiological Society has not endorsed the content of this adaptation or translation, or the context of its use.-
dc.subject.meshAcidosis - metabolism-
dc.subject.meshCalcium - metabolism-
dc.subject.meshIntracellular Membranes - metabolism-
dc.subject.meshMyocardium - cytology - metabolism-
dc.subject.meshReceptors, Opioid, kappa - agonists - physiology-
dc.titleAcidosis antagonizes intracellular calcium response to κ-opioid receptor stimulation in the rat heart-
dc.titleAcidosis antagonizes intracellular calcium response to kappa-opioid receptor stimulation in the rat heart-
dc.typeArticle-
dc.identifier.emailWong, TM: wongtakm@hkucc.hku.hk-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.pmid10484336-
dc.identifier.hkuros54107-
dc.identifier.volume277-
dc.identifier.issue3-
dc.identifier.spageC492-
dc.identifier.epageC500-
dc.publisher.placeUnited States-

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