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

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Marini P., Cowie P., AYAR A., Bewick G. S., Barrow J., Pertwee R. G., ...More

International Journal of Molecular Sciences, vol.24, no.2, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 24 Issue: 2
  • Publication Date: 2023
  • Doi Number: 10.3390/ijms24021308
  • Journal Name: International Journal of Molecular Sciences
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Keywords: intracellular calcium, M-3 receptor, CB1 receptor, CNR1 promoter, CREB, DELTA-OPIOID RECEPTOR, INTRACELLULAR CALCIUM, BINDING-PROTEIN, CANNABINOID CB1, ACETYLCHOLINE-RELEASE, MUSCARINIC RECEPTORS, ADENYLYL-CYCLASE, GENOME BROWSER, CYCLIC-AMP, EXPRESSION
  • Karadeniz Technical University Affiliated: Yes

Abstract

© 2023 by the authors.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. We show that M3 receptor-triggered calcium release greatly increases CB1 receptor expression via both transcriptional and translational activity, by enhancing CNR1 promoter activity. The co-expression of M3 and CB1 receptors in brain areas such as the nucleus accumbens and amygdala support the hypothesis that the altered synaptic plasticity observed after exposure to cannabinoids involves cross-talk with the M3 receptor subtype. In this context, M3 receptors and their interaction with the cannabinoid system at the transcriptional level represent a potential pharmacogenomic target not only for the develop of new drugs for addressing addiction and tolerance. but also to understand the mechanisms underpinning response stratification to cannabinoids.