Indomethacin Enhances Type 1 Cannabinoid Receptor Signaling.

ABSTRACT: In addition to its known actions as a non-selective cyclooxygenase (COX) 1 and 2 inhibitor, we hypothesized that indomethacin can act as an allosteric modulator of the type 1 cannabinoid receptor (CB1R) because of its shared structural features with the known allosteric modulators of CB1R. Indomethacin enhanced the binding of [³H]CP55940 to hCB1R and enhanced AEA-dependent [³⁵S]GTPγS binding to hCB1R in Chinese hamster ovary (CHO) cell membranes. Indomethacin (1 μM) also enhanced CP55940-dependent βarrestin1 recruitment, cAMP inhibition, ERK1/2 and PLCβ3 phosphorylation in HEK293A cells expressing hCB1R, but not in cells expressing hCB2R. Finally, indomethacin enhanced the magnitude and duration of CP55940-induced hypolocomotion, immobility, hypothermia, and anti-noci

SUBMITTER: Laprairie RB 

PROVIDER: S-EPMC6813218 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature