Cannabinoid 2 receptor- and beta Arrestin 2-dependent upregulation of serotonin 2A receptors

Franklin, Jade M.; Vasiljevik, Tamara; Prisinzano, Thomas E.; Carrasco, Gonzalo

doi:10.1016/j.euroneuro.2012.06.012

Cited by 22 publications

(38 citation statements)

References 34 publications

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“…Expression of GRK5, GRK2, GRK6, or CB 2 was determined by Western blot as described previously (3,4). GRK5, GRK2, GRK6, and CB 2 antibody was purchased from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA).…”

Section: Methodsmentioning

confidence: 99%

“…The specificity of these antibodies has been verified in the literature (24 -26). Films were analyzed densitometrically as described (3,4). All samples were standardized to controls and normalized to their respective actin levels.…”

Section: Methodsmentioning

confidence: 99%

“…Quantitative Real-time PCR-These reactions were prepared using the QuantiFast SYBR Green PCR kit (Qiagen, Valencia, CA) and the ABI 7500 fast real-time PCR system (Applied Biosystems, Foster City, CA), and then data were analyzed using the comparative cycle threshold (Ct) method as described previously (3,4). The primers used were as follows: 5-HT 2A (forward, 5Ј-AACGG-TCCATCCACAGAG-3Ј; reverse, 5Ј-AACAGGAAGAACACG-ATGC-3Ј), GRK5 (forward, 5Ј-GAACCACCAAAGAAAGGGC-TG-3Ј; reverse, 5Ј-CTAGCTGCTTCCAGTGGAG-3Ј), GRK2 (forward, 5Ј-GATGAGGAGACACAAAAGGAATC-3Ј; reverse, 5Ј-TCAGAGGCCGTTGGCACTGCCACGCTG-3Ј), GRK6 (forward, 5Ј-TTTGGGCTGGATGGGTCTGTTC-3Ј; reverse, 5Ј-C-GCTGCAGTTCCCACAGCAATC-3Ј), and GAPDH (forward, 5Ј-TGGAGTCTACTGGCGTCTTCAC-3Ј; reverse, 5Ј-GGCAT-GGACTGTGGTCATGA-3Ј).…”

Section: Methodsmentioning

confidence: 99%

“…This cannabinoid-mediated up-regulation of 5-HT 2A receptors was 1) induced by nonselective CB 1 /CB 2 and selective CB 2 receptor agonists (2, 4) and 2) inhibited by selective CB 2 , but not CB 1 , shRNA lentiviral particles, suggesting that CB 2 receptors mediate this phenomenon (3). Moreover, this up-regulation of 5-HT 2A receptors was ␤-arrestin 2-and ERK1/2-dependent because it was inhibited in cells stably transfected with ␤-arrestin 2 shRNA lentiviral particles (3) and by ERK1/2 inhibitors (2, 4).…”

mentioning

confidence: 98%

“…We have recently reported that repeated exposure to cannabinoid agonists induces a strong up-regulation and increases the activity of 5-HT 2A 2 receptors in rat prefrontal cortex (PFCx) and in two neuronal cell models (1)(2)(3)(4). This cannabinoid-mediated up-regulation of 5-HT 2A receptors was 1) induced by nonselective CB 1 /CB 2 and selective CB 2 receptor agonists (2, 4) and 2) inhibited by selective CB 2 , but not CB 1 , shRNA lentiviral particles, suggesting that CB 2 receptors mediate this phenomenon (3).…”

mentioning

confidence: 99%

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G-protein Receptor Kinase 5 Regulates the Cannabinoid Receptor 2-induced Up-regulation of Serotonin 2A Receptors

Franklin

Carrasco

2013

Journal of Biological Chemistry

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

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G-protein Receptor Kinase 5 Regulates the Cannabinoid Receptor 2-induced Up-regulation of Serotonin 2A Receptors

Franklin

Carrasco

2013

Journal of Biological Chemistry

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Cannabinoid receptor agonists upregulate and enhance serotonin 2A (5‐HT_2A) receptor activity via ERK1/2 signaling

Franklin

Carrasco

2012

Synapse

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Recent behavioral studies suggest that non-selective agonists of cannabinoid receptors may regulate serotonin 2A (5-HT2A) receptor neurotransmission. Two cannabinoids receptors are found in brain, CB1 and CB2 receptors, but the molecular mechanism by which cannabinoid receptors would regulate 5-HT2A receptor neurotransmission remains unknown. Interestingly, we have recently found that certain cannabinoid receptor agonists can specifically upregulate 5-HT2A receptors. Here, we present experimental evidence that rats treated with a non-selective cannabinoid receptor agonist (CP 55,940, 50μg/kg, 7 days) showed increases in 5-HT2A receptor protein levels, 5-HT2A receptor mRNA levels, and 5-HT2A receptor-mediated phospholipase C Beta (PLCβ) activity in prefrontal cortex (PFCx). Similar effects were found in neuronal cultured cells treated with CP 55,940 but these effects were prevented by selective CB2, but not selective CB1, receptor antagonists. CB2 receptors couple to the extracellular kinase (ERK) signaling pathway by Gαi/o class of G-proteins. Noteworthy, GP 1a (selective CB2 receptor agonist) produced a strong upregulation of 5-HT2A receptor mRNA and protein, an effect that was prevented by selective CB2 receptor antagonists and by an ERK1/2 inhibitor, PD 198306. In summary, our results identified a strong cannabinoid-induced upregulation of 5-HT2A receptor signaling in rat PFCx. Our cultured cell studies suggest that selective CB2 receptor agonists upregulate 5-HT2A receptor signaling by activation of the ERK1/2 signaling pathway. Activity of cortical 5-HT2A receptors has been associated with several physiological functions and neuropsychiatric disorders such as stress response, anxiety & depression and schizophrenia. Therefore, these results might provide a molecular mechanism by which activation of cannabinoid receptors might be relevant to the pathophysiology of some cognitive and mood disorders in humans.

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Pharmacological and Toxicological Effects of Synthetic Cannabinoids and Their Metabolites

Tai

Fantegrossi

2016

Neuropharmacology of New Psychoactive Substances (NPS)

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Commercial preparations containing synthetic cannabinoids (SCBs) are rapidly emerging as drugs of abuse. Although often assumed to be “safe” and “legal” alternatives to cannabis, reports indicate that SCBs induce toxicity not often associated with the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). This chapter will summarize the evidence that use of SCBs poses greater health risks relative to marijuana and suggest that distinct pharmacological properties and metabolism of SCBs relative to Δ9-THC may contribute to this increased toxicity. Studies reviewed will indicate that in contrast to partial agonist properties of Δ9-THC typically observed in vitro, SCBs act as full CB1 and CB2 receptor agonists both in cellular assays and animal studies. Furthermore, unlike Δ9-THC metabolism, several SCB metabolites retain high affinity for and exhibit a range of intrinsic activities at CB1 and CB2 receptors. Finally, the potential for SCBs to cause adverse drug–drug interactions with other drugs of abuse, as well as with common therapeutic agents, will be discussed. Collectively, the evidence provided in this chapter indicates that SCBs should not be considered safe and legal alternatives to marijuana. Instead, the enhanced toxicity of SCBs relative to marijuana, perhaps resulting from the combined actions of a complex mixture of different SCBs present and their active metabolites that retain high affinity for CB1 and CB2 receptors, highlights the inherent danger that may accompany use of these substances.

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Cannabinoid 2 receptor- and beta Arrestin 2-dependent upregulation of serotonin 2A receptors

Cited by 22 publications

References 34 publications

G-protein Receptor Kinase 5 Regulates the Cannabinoid Receptor 2-induced Up-regulation of Serotonin 2A Receptors

G-protein Receptor Kinase 5 Regulates the Cannabinoid Receptor 2-induced Up-regulation of Serotonin 2A Receptors

Cannabinoid receptor agonists upregulate and enhance serotonin 2A (5‐HT_2A) receptor activity via ERK1/2 signaling

Pharmacological and Toxicological Effects of Synthetic Cannabinoids and Their Metabolites

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Cannabinoid 2 receptor- and beta Arrestin 2-dependent upregulation of serotonin 2A receptors

Cited by 22 publications

References 34 publications

G-protein Receptor Kinase 5 Regulates the Cannabinoid Receptor 2-induced Up-regulation of Serotonin 2A Receptors

G-protein Receptor Kinase 5 Regulates the Cannabinoid Receptor 2-induced Up-regulation of Serotonin 2A Receptors

Cannabinoid receptor agonists upregulate and enhance serotonin 2A (5‐HT2A) receptor activity via ERK1/2 signaling

Pharmacological and Toxicological Effects of Synthetic Cannabinoids and Their Metabolites

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Cannabinoid receptor agonists upregulate and enhance serotonin 2A (5‐HT_2A) receptor activity via ERK1/2 signaling