Results for “Receptor, Cannabinoid, CB1”

PubMed2026

Transcriptional Mapping of the Human Cannabinoid Receptor 1 (CNR1) Gene Promoter.

The transcriptional regulation of the cannabinoid receptor 1 (CB1R) by promoter/enhancer elements and transcription factors is an area of cannabinoid research that has historically been understudied. To map the promoter region of the human CNR1 gene (the gene encoding CB1R), a 997-base-pair fragment from the sequence upstream of the CNR1 gene was cloned into a secreted luciferase reporter vector, and a series of deletion fragments were constructed. The transcriptional activity of these constructs was tested in human cell lines from three tissues: neuronal tissue (SHSY5Y), kidney tissue (HEK293T), and colonic epithelium (HCT116). Through this mapping, we have identified two key regulatory regions within the promoter. Increased levels of cAMP suppressed reporter expression from the full-length promoter fragment in all three cell lines, and in silico modeling predicts potential cAMP response elements (CRE) within one of the key regulatory sequences. Additionally, the minimal promoter region for CNR1 also appears to be in the second regulatory region identified, and in silico modeling predicts BRE and INR elements within this sequence. These findings begin to unravel the mechanisms by which CNR1 is transcriptionally regulated.

Humans↗

PubMed2025

Stress reactivity is modulated by cannabinoid type-1 receptors in norepinephrine and epinephrine neurons in a context-dependent manner.

Disruptions in the endocannabinoid system (ECS) and norepinephrine/epinephrine (NE/E) system are individually linked to stress-related neuropsychiatric disorders, but their interaction in shaping stress responses remains unclear. We investigated the role of the ECS's primary receptor, cannabinoid type-1 receptor (CB1R), in NE/E-producing neurons using anatomical, behavioral, and physiological analyses in a conditional knockout mouse model (Cnr1cKO-Dbh), in which the Cnr1 gene-encoding CB1R-was selectively deleted in dopamine beta-hydroxylase-expressing cells. In situ hybridization in control mice revealed Cnr1 is broadly expressed in medullary C1/A1 and C2/A2 and sparsely in the locus coeruleus, marking the first cell-type-specific characterization of Cnr1 in brainstem catecholaminergic populations. Cnr1 was reduced across all nuclei in Cnr1cKO-Dbh mice, confirming targeted deletion. Behaviorally, Cnr1cKO-Dbh mice showed normal baseline anxiety-like behavior, but reduced avoidance in the open field after acute restraint stress. However, no genotype differences were found after foot shock in the elevated plus maze and light-dark box, suggesting context-dependent CB1R effects. Cnr1cKO-Dbh mice also exhibited reduced immobility in the forced swim test, but not the tail suspension test. In response to looming visual threats, they showed increased escape behavior across trials, reduced rearing and exploration during the first disc presentation, and no changes in freezing. Heart rate responses following foot shock stress were unchanged. These findings suggest that CB1R in NE/E neurons selectively modulate components of the acute stress response in a manner dependent on behavioral context. This work underscores the need for further investigation into the circuit- and state-specific roles of CB1R signaling in stress regulation.

Animals↗