Cannabinoid 1 receptors are expressed in nociceptive primary sensory neurons

Ahluwalia, Jatinder; Urbán, László; Capogna, Marco; Bevan, Stuart; Nagy, I.

doi:10.1016/s0306-4522(00)00389-4

Cited by 279 publications

(217 citation statements)

References 31 publications

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“…As the effect of anandamide on both TRPV1 and CB 1 receptors is regulated by FAAH hydrolysis and cellular uptake by the putative anandamide transporter (Hillard, 2000), it is possible that inhibition of anandamide hydrolysis and reuptake by cannabidiol could lead to potentiation of the activity of anandamide at both TRPV1 and CB 1 receptors. Coexpression of CB 1 and TRPV1 receptors has been demonstrated in rat dorsal root ganglion neurons (Ahluwalia et al, 2000;Bridges et al, 2003) and in rat mesencephalic cultures (Kim et al, 2005). Tonic activation of CB 1 receptors exerts an inhibitory control over TRPV1 receptors, as anandamide or capsaicin-induced TRPV1 receptor-mediated effects are potentiated in the presence of a CB 1 receptor antagonist (Maccarrone et al, 2000;Mang et al, 2001;Lever and Malcangio, 2002).…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol Reverses MK-801-Induced Disruption of Prepulse Inhibition in Mice

Long

Malone

Taylor

2005

Neuropsychopharmacol

151

102

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Cannabidiol, a nonpsychoactive constituent of the Cannabis sativa plant, has been reported to act as an agonist of the vanilloid 1 channel in the transient receptor potential family (TRPV1) and also to inhibit the hydrolysis and cellular uptake of the endogenous cannabinoid anandamide. Cannabidiol has also been reported to have potential as an antipsychotic. We investigated the effect of cannabidiol on sensorimotor gating deficits in mice induced by the noncompetitive NMDA receptor antagonist, MK-801. Sensorimotor gating is deficient in psychotic disorders such as schizophrenia and may be reliably measured by prepulse inhibition (PPI) of the startle response in rodents and humans. MK-801 (0.3-1 mg/kg i.p.) dose dependently disrupted PPI while cannabidiol (1-15 mg/kg i.p.), when administered with vehicle, had no effect on PPI. Cannabidiol (5 mg/kg i.p.) successfully reversed disruptions in PPI induced by MK-801 (1 mg/kg i.p.), as did the atypical antipsychotic clozapine (4 mg/kg i.p.). Pretreatment with capsazepine (20 mg/kg i.p.) prevented the reversal of MK-801-induced disruption of PPI by cannabidiol, providing preliminary evidence that TRPV1 receptors are involved in the reversal of MK-801-induced sensorimotor gating deficits by cannabidiol.

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Section: Discussionmentioning

confidence: 99%

Cannabidiol Reverses MK-801-Induced Disruption of Prepulse Inhibition in Mice

Long

Malone

Taylor

2005

Neuropsychopharmacol

151

102

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“…The expression of both receptors was not confined only to neurons, but has been reported also in astrocytes for TRPV1 and in glial cells for CB1-R (Doyle et al, 2002;Toth et al, 2005;Pazos et al, 2005). In addition, there is evidence of a high degree of colocalization of CB1-R and TRPV1 in DRG neurons, enriched mesencephalic cultures, hippocampus, and cerebellum (Ahluwalia et al, 2000(Ahluwalia et al, , 2002Kim et al, 2005;Cristino et al, 2006). However, there have been no reports on the colocalization of both receptors at synaptic level.…”

Section: Introductionmentioning

confidence: 93%

N-Arachidonoyl-Dopamine Tunes Synaptic Transmission onto Dopaminergic Neurons by Activating both Cannabinoid and Vanilloid Receptors

Marinelli

Marzo

Florenzano

et al. 2006

Neuropsychopharmacol

148

117

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In the present study, we used electrophysiological, biochemical, and confocal microscopy techniques, to investigate the functional role of transient receptor potential vanilloid type 1 (TRPV1) and cannabinoid type 1 receptors (CB1-R) in the substantia nigra pars compacta (SNpc) and their stimulation by the endocannabinoid N-arachidonoyl-dopamine (NADA). Liquid chromatography-mass spectrometry analyses revealed that a NADA-like compound is produced in substantia nigra slices, in conditions of hyperactivity. Moreover, the functional role of both TRPV1 and CB1-R in modulating synaptic transmission in this area was suggested by confocal microscopy data, showing TRPV1 and CB1-R immunoreactivity in punctate structures, probably representing synaptic contacts on cell bodies of the SNpc. In patch-clamp recordings from dopamine (DA) neurons of the SNpc, we found that NADA increases or reduces glutamatergic transmission onto DA neurons by activating TRPV1 and CB1 receptors, respectively, whereas it decreases GABAergic transmission via CB1 stimulation. Facilitation of glutamate release through TRPV1 was blocked in the presence of a selective blocker of the putative endocannabinoid membrane transporter (EMT), indicating that NADA needs to be taken up by cells to interact with this receptor. In line with these data, biochemical results demonstrated that NADA selectively acted at CB1-R when its re-uptake was blocked. Altogether these data demonstrate a significant role exerted by the endocannabinoid/endovanilloid NADA in the regulation of synaptic transmission to DA neurons of the SNpc. Moreover, they highlight a key function of the EMT transporter in promoting the stimulation of TRPV1 or CB1-R, thus favoring facilitation or inhibition of glutamate synaptic release.

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“…Pharmacological, genetic and anatomical evidence indicates that cannabinoid CB receptors ex-1 Ž pressed in nociceptive neurons Hohmann and Herkenham, . 1999;Ahluwalia et al, 2000 are involved in the periph-Ž eral actions of cannabinoid drugs Calignano et al, 1998; . Richardson et al, 1998;Zimmer et al, 1999 .…”

Section: Introductionmentioning

confidence: 99%