CP55,940 increases intracellular Ca2+ levels in Madin-Darby canine kidney cells

Chou, Kang Ju; Tseng, Li Ling; Cheng, Jin; Wang, Jue Long; Fang, Hua; Lee, Kam Chung; Su, Warren; Law, Yee Ping; Jan, Chung Ren

doi:10.1016/s0024-3205(01)01242-5

Cited by 10 publications

(6 citation statements)

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“…Although a functional response of canine tubular renal cells to the CB agonist CP55,940 has been reported, it was not blocked by CB antagonists, suggesting that the response was dissociated from the activation of CB receptors (Chou et al, 2001). Moreover, the renal expression of CB receptors and the AEA-degrading enzyme, FAAH, was found to be associated with the vasculature (Deutsch et al, 1997).…”

Section: Discussionmentioning

confidence: 95%

Modulation of P‐glycoprotein activity by cannabinoid molecules in HK‐2 renal cells

Nieri

Romiti

Adinolfi

et al. 2006

British J Pharmacology

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1 Endogenous and synthetic cannabinoid molecules have been investigated as possible MDR-1/Pglycoprotein (P-gp) modulators in HK-2-immortalized renal cells, using calcein acetoxymethylester (calcein-AM) as a P-gp substrate.2 Among the endocannabinoid molecules tested, anandamide (AEA), but not 2-arachidonoylglycerol (2-AG) or palmitoyl-ethanolamide (PEA), increased the intracellular fluorescence emitted by calcein, a metabolic derivative of the P-gp substrate calcein-AM, indicative of a reduction in transport capacity. 3 All the three synthetic cannabimimetics tested, that is, R-( þ )-methanandamide (R( þ )-MET), AM 251 and CP55,940 significantly increased calcein accumulation in the cytosol. 4 RT-PCR demonstrated that HK-2 cells do not express CB 1 or CB 2 cannabinoid receptors. 5 R( þ )-MET, AM251 and CP55,940 were also evaluated as modulators of P-gp expression, by Western blot analysis. Only AM251 weakly enhanced the protein levels (by 1.2-fold) after a 4-day-long incubation with the noncytotoxic drug concentration 2 mM. 6 The present data provide the first evidence that the endocannabinoid AEA and different synthetic cannabinoids may inhibit the P-gp activity in vitro via a cannabinoid receptor-independent mechanism.

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Section: Discussionmentioning

confidence: 95%

Modulation of P‐glycoprotein activity by cannabinoid molecules in HK‐2 renal cells

Nieri

Romiti

Adinolfi

et al. 2006

British J Pharmacology

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“…In Madin-Darby canine kidney cells CP 55,940 increased [Ca 2+ ] i in a concentration-dependent manner (Chou et al, 2001). CP 55,940 was shown to release Ca 2+ from thapsigargin (an endoplasmic reticulum Ca 2+ ATPase inhibitor)-sensitive stores in an InsP 3 -independent manner, as the response was not altered by U73122.…”

Section: Modulation Of Intracellular Ca 2+ Concentration ([Ca 2+ ] I )mentioning

confidence: 95%

Cannabinoid signalling

Demuth¹,

Molleman²

2006

Life Sciences

387

328

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“…As cannabinoids have been shown to promote changes in Ca 2+ homeostasis, we investigated the influence of CBD treatment on [Ca 2+ ] i levels in human articular chondrocytes. We were able to demonstrate a sustained elevation of [Ca 2+ ] i after CBD treatment in live‐cell imaging experiments.…”

Section: Discussionmentioning

confidence: 99%

Dose‐Dependent Cannabidiol‐Induced Elevation of Intracellular Calcium and Apoptosis in Human Articular Chondrocytes

Winklmayr

Gaisberger

Kittl

et al. 2019

Journal Orthopaedic Research

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Cannabidiol (CBD) is the most abundant non‐psychoactive compound of Cannabis sativa extracts. Cannabinoids have been shown to exhibit anti‐inflammatory, analgesic, antioxidant, neuroprotective, and anti‐tumorigenic effects. In the present study, we investigated the effects of CBD on human articular chondrocytes. Cell viability was determined by Resazurin assays. Apoptosis was analyzed by annexin‐V/7‐actinomycin D (7‐AAD) staining followed by flow cytometry. Caspase 3/7 activity was measured with caspase assays. Intracellular Ca2+ ([Ca2+]i) was monitored by time‐lapse fluorescence imaging. The perforated whole‐cell patch‐clamp technique was used for measuring the cell membrane potential. Erk1/2 phosphorylation was assessed by western blot analysis. The chondrocyte cell line C28/I2 and primary chondrocytes showed a reduced viability after treatment with concentrations of CBD greater than 4 µM. This apoptotic effect was accompanied by an increase of caspase 3/7 activity and an increase in the early apoptotic cell population. CBD elevated [Ca2+]i, which was accompanied by depolarization of the cell membrane potential. The increase of [Ca2+]i was abrogated, when Ca2+ was omitted from the bath solution, indicating an influx of extracellular Ca2+. The cannabinoid receptor 1 (CB1) antagonist AM251 inhibited the Ca2+ influx triggered by CBD. Preincubation with AM251 reduced the toxic effects of CBD. By looking for mediators of the apoptotic CBD effect downstream of the CB1 receptor, enhanced Erk1/2 phosphorylation could be detected after CBD treatment. However, this Erk1/2 activation proved to be unaffected by CB1 receptor blockage. The present study demonstrates that CBD promotes apoptosis and [Ca2+]i elevation in human articular chondrocytes via a CB1‐receptor‐mediated mechanism. © 2019 The Authors. Journal of Orthopaedic Research ® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 37:2540–2549, 2019

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CP55,940 increases intracellular Ca2+ levels in Madin-Darby canine kidney cells

Cited by 10 publications

References 0 publications

Modulation of P‐glycoprotein activity by cannabinoid molecules in HK‐2 renal cells

Modulation of P‐glycoprotein activity by cannabinoid molecules in HK‐2 renal cells

Cannabinoid signalling

Dose‐Dependent Cannabidiol‐Induced Elevation of Intracellular Calcium and Apoptosis in Human Articular Chondrocytes

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