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Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production

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Abstract

Delta-9-tetrahydrocannabinol (THC), the major active component of marijuana, has a beneficial effect on the cardiovascular system during stress conditions, but the defence mechanism is still unclear. The present study was designed to investigate the central (CB1) and the peripheral (CB2) cannabinoid receptor expression in neonatal cardiomyoctes and possible function in the cardioprotection of THC from hypoxia. Pre-treatment of cardiomyocytes that were grown in vitro with 0.1 – 10 μM THC for 24 h prevented hypoxia-induced lactate dehydrogenase (LDH) leakage and preserved the morphological distribution of α-sarcomeric actin. The antagonist for the CB2 (10 μM), but not CB1 receptor antagonist (10 μM) abolished the protective effect of THC. In agreement with these results using RT-PCR, it was shown that neonatal cardiac cells express CB2, but not CB1 receptors. Involvement of NO in the signal transduction pathway activated by THC through CB2 was examined. It was found that THC induces nitric oxide (NO) production by induction of NO synthase (iNOS) via CB2 receptors. L-NAME (NOS inhibitor, 100 μM) prevented the cardioprotection provided by THC. Taken together, our findings suggest that THC protects cardiac cells against hypoxia via CB2 receptor activation by induction of NO production. An NO mechanism occurs also in the classical pre-conditioning process; therefore, THC probably pre-trains the cardiomyocytes to hypoxic conditions.

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Authors and Affiliations

  1. Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel

    Yelena A. Shmist, Igor Goncharov, Vladimir Shneyvays, Ahuva Isaac & Asher Shainberg

  2. Weizmann Institute of Science, Rehovot, Israel

    Maor Eichler & Zvi Vogel

  3. Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel

    Asher Shainberg

Authors
  1. Yelena A. Shmist
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  2. Igor Goncharov
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  3. Maor Eichler
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  4. Vladimir Shneyvays
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  5. Ahuva Isaac
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  6. Zvi Vogel
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  7. Asher Shainberg
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Correspondence to Asher Shainberg.

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Shmist, Y.A., Goncharov, I., Eichler, M. et al. Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production. Mol Cell Biochem 283, 75–83 (2006). https://doi.org/10.1007/s11010-006-2346-y

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  • DOI: https://doi.org/10.1007/s11010-006-2346-y

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