Spatial Distribution of the Cannabinoid Type 1 and Capsaicin Receptors May Contribute to the Complexity of Their Crosstalk

Jie Chen; Angelika Varga; Srikumaran Selvarajah; Agnes Jenes; Beatrix Dienes; Joao Sousa-Valente; Akos Kulik; Gabor Veress; Susan D Brain; David Baker; Laszlo Urban; Ken Mackie; Istvan Nagy

doi:10.1038/srep33307

Spatial Distribution of the Cannabinoid Type 1 and Capsaicin Receptors May Contribute to the Complexity of Their Crosstalk

Sci Rep. 2016 Sep 22:6:33307. doi: 10.1038/srep33307.

Authors

Jie Chen^{1

2}, Angelika Varga^{1

3}, Srikumaran Selvarajah¹, Agnes Jenes^{1

3}, Beatrix Dienes³, Joao Sousa-Valente¹, Akos Kulik^{4

5}, Gabor Veress⁶, Susan D Brain⁷, David Baker⁸, Laszlo Urban⁹, Ken Mackie¹⁰, Istvan Nagy¹

Affiliations

¹ Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.
² Department of Anaesthesiology, Southwest Hospital, Third Military Medical University, Gaotanyan 19 Street, Shapingba, Chongqing 400038, P. R. China.
³ MTA-DE-NAP B-Pain Control Research GroupDepartment of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4012, Hungary.
⁴ Institute of Physiology, University of Freiburg, Germany D-79104 Freiburg, Germany.
⁵ BIOSS Centre for Biological Signalling Studies, University of Freiburg, D-79104, Germany.
⁶ Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
⁷ BHF Cardiovascular Centre of Excellence and Centre of Integrative Biomedicine, Cardiovascular Division, King's College London, London SE1 9NH, UK.
⁸ Centre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
⁹ Preclinical Secondary Pharmacology, Preclinical Safety, Novartis Institutes for Biommedical Research, Cambridge, MA 01932, USA.
¹⁰ Department of Psychological and Brain Sciences and Program in Neuroscience, Indiana University, The Gill Center, 702 N. Walnut Grove Avenue, Bloomington, IN 47405, USA.

Abstract

The cannabinoid type 1 (CB1) receptor and the capsaicin receptor (TRPV1) exhibit co-expression and complex, but largely unknown, functional interactions in a sub-population of primary sensory neurons (PSN). We report that PSN co-expressing CB1 receptor and TRPV1 form two distinct sub-populations based on their pharmacological properties, which could be due to the distribution pattern of the two receptors. Pharmacologically, neurons respond either only to capsaicin (COR neurons) or to both capsaicin and the endogenous TRPV1 and CB1 receptor ligand anandamide (ACR neurons). Blocking or deleting the CB1 receptor only reduces both anandamide- and capsaicin-evoked responses in ACR neurons. Deleting the CB1 receptor also reduces the proportion of ACR neurons without any effect on the overall number of capsaicin-responding cells. Regarding the distribution pattern of the two receptors, neurons express CB1 and TRPV1 receptors either isolated in low densities or in close proximity with medium/high densities. We suggest that spatial distribution of the CB1 receptor and TRPV1 contributes to the complexity of their functional interaction.