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 1 Endogenous and synthetic cannabinoid molecules have been investigated as possible MDR‐1/P‐glycoprotein (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‐arachidonoyl‐glycerol (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‐(+)‐methanandamide (R(+)‐MET), AM 251 and CP55,940 significantly increased calcein accumulation in the cytosol. 4 RT–PCR demonstrated that HK‐2 cells do not express CB1 or CB2 cannabinoid receptors. 5 R(+)‐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 μM. 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. British Journal of Pharmacology (2006) 148, 682–687. doi:10.1038/sj.bjp.0706778 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

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

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Publisher
Wiley
Copyright
2006 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1038/sj.bjp.0706778
pmid
16715117
Publisher site
See Article on Publisher Site

Abstract

1 Endogenous and synthetic cannabinoid molecules have been investigated as possible MDR‐1/P‐glycoprotein (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‐arachidonoyl‐glycerol (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‐(+)‐methanandamide (R(+)‐MET), AM 251 and CP55,940 significantly increased calcein accumulation in the cytosol. 4 RT–PCR demonstrated that HK‐2 cells do not express CB1 or CB2 cannabinoid receptors. 5 R(+)‐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 μM. 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. British Journal of Pharmacology (2006) 148, 682–687. doi:10.1038/sj.bjp.0706778

Journal

British Journal of PharmacologyWiley

Published: Jul 1, 2006

References

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