Schematic illustration showing the relationship between hypothalamic peptidergic circuits that express CB1 receptors (yellow cirlces), as described by Cota et al. (9), and some of those that do not. The former include cells that produce CART and pro-opiomelanocortin (POMC) in the arcuate nucleus (ARC); neurons that express MCH (blue) and orexin (ORX; red) in the lateral hypothalamic (LH) region; and neurons that produce CRH (brown) in the paraventricular nucleus (PVN). CB1 receptors are produced in the cytosol of these cells (yellow circles outlined in black) and are transported (white arrows) to axon terminals. Here, the receptors, upon activation (black arrowheads) by endocannabinoids (ECB) or other agonists, are thought to affect the release of neuromodulators (MCH, ORX, CART, corticotropin-releasing factor) to the synaptic cleft. A population of neurons in the medial arcuate nucleus produces neuropeptide Y (NPY) and agouti-related protein (AgRP), both of which are considered regulators of energy homeostasis. The NPY/AgRP–producing neurons, as well as those that produce ghrelin (GHR), were not found to contain CB1 receptors (9). GHR is also produced in the stomach and, together with the adipose hormone leptin, reaches hypothalamic peptidergic circuits via the circulation. The source of endocannabinoids in the hypothalamus is yet to be determined. Similarly, the hierarchical relationship between CB1-containing axon terminals and other axon terminals and their postsynaptic targets needs to be established to allow a better understanding of the hypothalamic signaling of cannabinoids. Putative inhibitory (–) and stimulatory (+) influences on food intake of the various elements of the peptidergic system are shown. Note that this influence on food intake may not reflect electrophysiological effects of the respective peptides. III, third ventricle.
Tamas L. Horvath. Endocannabinoids and the regulation of body fat: the smoke is clearing. J. Clin. Invest. 112:323-326 (2003)

Cellular source and proposed targets of anti-inflammatory endocannabinoids in IBD.
(a) Cross-section of inflamed bowel with leukocyte infiltration (polymorphonuclear, lymphocytes, macrophages, mast cells). (b) In macrophages, LPS induces the production of TNF and chemokines (such as MIP-2 and CXCL-8) as well as anandamide. Anandamide is released to act as an autocrine mediator to inhibit TNF and chemokine production via CB1 or CB2 receptors or both. Activation of CB1 and CB2 receptors may similarly inhibit TNF production in mast cells, with these effects resulting in decreased leukocyte infiltration and inflammation. Paracrine activation of CB1 receptors on extrinsic and intrinsic enteric neurons inhibits acetylcholine and tachykinin release, respectively, resulting in inhibition of gut motility. These effects are amplified by treatment with a FAAH inhibitor, which prevents the breakdown of anandamide.
Deborah Maizels from Nature Medicine  10, 678 - 679 (2004)

A, Presence of CB1 and CB2 mRNAs in a rat mast cell line. Northern blot analysis of CB1 and CB2 transcript levels was performed using 32P-labeled probes as described in Materials and Methods. Poly(A)+ mRNA (1 µg/lane) was used to prepare multiple cell line Northern blot membranes. Cell types used were: B, Ramos B lymphocytes; T, Jurkat T lymphocytes; NI, nonimmune human embryonic kidney endothelial cells; and M, RBL2H3 mast cell. Size markers are shown in kb. B, Western blot analysis of CB1 and CB2 protein levels in mast and neuronal cell backgrounds. Acetone-precipitated protein was prepared from replicate samples of 5 x 106 cells/lane of the indicated cell line. Proteins were resolved by SDS-PAGE and Western blotted using anti-CB1 or anti-CB2 antisera . Molecular mass markers are shown in kDa. Lower panels, Migration distance plotted against molecular mass to enable estimation of molecular mass for the CB1 and CB2 receptors. The trend line was generated using the estimated midpoint for each molecular mass marker and CB receptor band.
Samson M-T. , et al., The Journal of Immunology, 2003, 170: 4953-4962.

Cannabinoid receptor immunoreactivity in first trimester placenta. A, Rat cerebellum was used as a positive control for CB1 immunoreactivity. Consistent with previous reports (27 ), CB1 immunoreactivity was strong in the molecular layer (ML) and in basket cells (BC), but was absent from the granule cell layer (Gr; x25 objective). B, No CB1-positive immunoreactivity was identified in first trimester placental samples (x25 objective). C and D, CB2-positive labeling was observed in only a subset of cells within the villous stroma (arrows; x63 and x100 objectives, respectively). These cells were identified as villous macrophages by double immunofluorescence labeling with antibodies to CB2 (red; E) and CD14 (green; F). G, Hoechst-stained nuclei (blue). H, Double labeling demonstrating colocalization of these signals (yellow; x100 objective).
Helliwell R. J. A. et al.,The Journal of Clinical Endocrinology & Metabolism , 2004, Vol. 89, No. 10 5168-5174

Western blots of CB1 (lanes 1, 2), FAAH (lanes 3, 4), and CB2 (lanes 5, 6) immunoreactivities in human temporal cortex from an AD patient. Single bands of ~50 kDa (CB1 and FAAH) or 60 kDa (CB2) were observed (lanes 1, 3, and 5, respectively). No immunoreactivities were detected when the primary antibodies were preincubated with the respective immunizing peptides (lanes 2, 4, and 6).
Benito C., et al. The Journal of Neuroscience, December 3, 2003, 23(35):11136-11141

FAAH and CB2 are expressed in glial cells associated with -amyloid-enriched neuritic plaques. A, B, FAAH (brown) and -amyloid peptide (blue) stainings. Note that FAAH-positive cells are astrocytes surrounding -amyloid-enriched plaques. C, D, CB2 (brown) and -amyloid peptide (blue) stainings. CB2 immunostaining is limited to plaque-associated microglial cells.
Benito C., et al. The Journal of Neuroscience, December 3, 2003, 23(35):11136-11141

CB2 (A-C, E) and CD68 (D) stainings in parahippocampal cortex. A, CB2 staining in a healthy individual sample. No detectable signal could be seen. B, Low and high (inset) magnifications of CB2 immunoreactivity in parahippocampal cortex of an AD case. Note the intense signal for CB2 in microglial cells located on neuritic plaques. C, Detail of CB2 immunoreactivity in neuritic plaque-associated microglia. D, Low and high (inset) magnification of CD68 immunoreactivity in an AD case. E, CB2 staining after preabsorption and coincubation of the antibody with the immunizing peptide. Note the absence of any detectable signal. Scale bars: A, B, D, E, 800 µm; insets in B and D, 200 µm; C, 100 µm.
Benito C., et al. The Journal of Neuroscience, December 3, 2003, 23(35):11136-11141