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Research Article 2023CC BYFree full text

M3 Receptor Pathway Stimulates Rapid Transcription of the CB1 Receptor Activation through Calcium Signalling and the CNR1 Gene Promoter.

Pietro Marini, Philip Cowie, Ahmet Ayar, Guy S Bewick, John Barrow, Roger G Pertwee +3 more

In this study, we have investigated a possible mechanism that enables CB1/M3 receptor cross-talk, using SH-SY5Y cells as a model system. Our results show that M3 receptor activation initiates signaling that rapidly upregulates the CNR1 gene, resulting in a greatly potentiated CB1 receptor response to agonists. Calcium homeostasis plays an essential intermediary role in this functional CB1/M3 receptor cross-talk. W…

International Journal of Molecular Sciences Europe PMC

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Research Article 2020CC BYFree full text

Disease-associated polymorphisms within the conserved ECR1 enhancer differentially regulate the tissue-specific activity of the cannabinoid-1 receptor gene promoter; implications for cannabinoid pharmacogenetics.

Elizabeth A Hay, Philip Cowie, Andrew R McEwan, Ruth Ross, Roger G Pertwee, Alasdair MacKenzie

Cannabinoid receptor-1 (CB1) represents a potential drug target against conditions that include obesity and substance abuse. However, drug trials targeting CB1 (encoded by the CNR1 gene) have been compromised by differences in patient response. Toward addressing the hypothesis that genetic changes within the regulatory regions controlling CNR1 expression contribute to these differences, we characterized the effect…

Human Mutation