Pre- and postsynaptic localizations of the CB1 cannabinoid receptor in the dorsal horn of the rat spinal cord

Salio, Chiara; Fischer, Jacqueline; Franzoni, Maria Fosca; Conrath, M.

doi:10.1016/s0306-4522(01)00584-x

Cited by 100 publications

(85 citation statements)

References 64 publications

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“…Of note, we observed that immunoreactivity for CB 1 is also particularly dense in the superficial lamina I of the spinal dorsal horn (Fig. 6 B, arrowhead), consistent with previous reports (Salio et al, 2002). In addition to cell bodies in the superficial laminas, a large part of the GASP1 immunoreactivity was found in the neuropil, reflecting that spinal terminals of nociceptive primary afferent fibers, which densely innervate this region, could harbor cGASP1.…”

Section: Expression Of Gasp1 In the Spinal Sensorimotor Circuit Procesupporting

confidence: 91%

A Molecular Basis of Analgesic Tolerance to Cannabinoids

Tappe‐Theodor

Agarwal

Katona³

et al. 2007

J. Neurosci.

102

108

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Clinical usage of cannabinoids in chronic pain states is limited by their central side effects and the pharmacodynamic tolerance that sets in after repeated dosage. Analgesic tolerance to cannabinoids in vivo could be caused by agonist-induced downregulation and intracellular trafficking of cannabinoid receptors, but little is known about the molecular mechanisms involved. We show here that the type 1 cannabinoid receptor (CB 1 ) interacts physically with G-protein-associated sorting protein 1 (GASP1), a protein that sorts receptors in lysosomal compartments destined for degradation. CB 1 -GASP1 interaction was observed to be required for agonist-induced downregulation of CB 1 in spinal neurons ex vivo as well as in vivo. Importantly, uncoupling CB 1 from GASP1 in mice in vivo abrogated tolerance toward cannabinoid-induced analgesia. These results suggest that GASP1 is a key regulator of the fate of CB 1 after agonist exposure in the nervous system and critically determines analgesic tolerance to cannabinoids.

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Section: Expression Of Gasp1 In the Spinal Sensorimotor Circuit Procesupporting

confidence: 91%

A Molecular Basis of Analgesic Tolerance to Cannabinoids

Tappe‐Theodor

Agarwal

Katona³

et al. 2007

J. Neurosci.

102

108

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“…The absence of codistribution of CGRP with CB1 receptors within fibers is consistent with observations made with an antibody directed against the C terminus of the receptor (Farquhar-Smith et al, 2000). Whereas immunoreactivity in lamina I is likely to be associated with axons, CB1 receptor-ir in deeper layers is most likely associated with dendrites and cell bodies of spinal interneurons (Farquhar-Smith et al, 2000;Salio et al, 2002). Only DOR-ir demonstrated a high colocalization with CGRP-ir.…”

Section: Modulation Of Cgrp Releasesupporting

confidence: 86%

Differential Effects of CB1 and Opioid Agonists on Two Populations of Adult Rat Dorsal Root Ganglion Neurons

Khasabova

Harding-Rose

Simone³

et al. 2004

J. Neurosci.

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“…Although postsynaptic CB 1 receptors have been suggested to exist in the brain (2,35,(42)(43)(44), there is no evidence that CB 1 receptors located postsynaptically influence GABA transporter function. Furthermore, Vaughan et al (53) did not find postsynaptic cannabinoid inhibition in the PAG, which is consistent with the observation of a high prevalence of CB 1 receptors on PAG axons and fibers rather than cell bodies (52).…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB₁ receptors

Fu¹,

Longhurst²

2009

Journal of Applied Physiology

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Fu L-W, Longhurst JC. Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB1 receptors. J Appl Physiol 106: 1800 -1809, 2009. First published April 9, 2009 doi:10.1152/japplphysiol.91648.2008.-Previous studies have demonstrated that electroacupuncture (EA) attenuates sympathoexcitatory reflex responses by activating a long-loop pathway involving the hypothalamic arcuate nucleus (ARC), midbrain ventrolateral periaqueductal gray (vlPAG), and rostral ventrolateral medulla (rVLM). Neurons in the ARC provide excitatory input to the vlPAG, whereas the vlPAG inhibits neuronal activity in the rVLM. ␥-Aminobutyric acid (GABA) and glutamate (Glu) have been identified in the vlPAG. Endocannabinoids (ECs), acting as atypical neurotransmitters, inhibit the release of both neurotransmitters in the hypothalamus and midbrain through a presynaptic cannabinoid type 1 (CB1) receptor mechanism. The EC system has been observed in the dorsal but not in the vlPAG. Since it is uncertain whether ECs influence GABA and Glu in the vlPAG, the present study tested the hypothesis that EA modulates the release of these neurotransmitters in the vlPAG through a presynaptic CB1 receptor mechanism. We measured the release of GABA and Glu simultaneously by using HPLC to assess samples collected with microdialysis probes inserted unilaterally into the vlPAG of intact anesthetized rats. Twenty-eight min of EA (2 Hz, 2-4 mA, 0.5 ms) at the P5-6 acupoints reduced the release of GABA by 39% during EA and by 44% 15 min after EA. Thirty-five minutes after EA, GABA concentrations returned to pre-EA levels. In contrast, sham EA did not change the vlPAG GABA concentration. Blockade of CB1 receptors with AM251, a selective CB1 receptor antagonist, reversed the EA-modulated changes in GABA concentration, whereas microinjection of vehicle into the vlPAG did not alter EA-modulated GABA changes. In addition, we observed no changes in the vlPAG Glu concentrations during EA, although the baseline concentration of Glu was much higher than that of GABA (3,541 Ϯ 373 vs. 33.8 Ϯ 8.7 nM, Glu vs. GABA). These results suggest that EA modulates the sympathoexcitatory reflex responses by decreasing the release of GABA, but not Glu, in the vlPAG, most likely through a presynaptic CB1 receptor mechanism. somatic afferents; sympathoexcitatory reflex; cannabinoid type 1 receptor; microdialysis ELECTROACUPUNCTURE (EA), a potent alternative to manual acupuncture, has been suggested to be effective in treating certain cardiovascular diseases including hypertension, arrhythmias, and angina pectoris (5, 6, 41). Clinically, EA at the NeiguanJianshi (P5-6) acupoints has been used to treat cardiovascular diseases in Eastern and, more recently, Western countries (5, 21, 41). We and others have demonstrated that EA at P5-6 acupoints overlying the median nerve on the wrist modulate blood pressure elevation evoked by gastric distension (GD) in rats (27) or by gallbladder stimulation in cats (50) through a long-loop neural pathway, extending from the arcuate...

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Pre- and postsynaptic localizations of the CB1 cannabinoid receptor in the dorsal horn of the rat spinal cord

Cited by 100 publications

References 64 publications

A Molecular Basis of Analgesic Tolerance to Cannabinoids

A Molecular Basis of Analgesic Tolerance to Cannabinoids

Differential Effects of CB1 and Opioid Agonists on Two Populations of Adult Rat Dorsal Root Ganglion Neurons

Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB₁ receptors

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