Molecular cloning of a human cannabinoid receptor which is also expressed in testis

Gérard, Claude; Mollereau, Catherine; Vassart, Gilbert; Parmentier, Marc

doi:10.1042/bj2790129

Cited by 623 publications

(349 citation statements)

References 20 publications

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“…20,27,45 Namely, CB1 was expressed in interneuron types characterized by the presence of the neuropeptide CCK. Taken together with the surprisingly conserved structure of the CB1 gene in mammals, 2,9,13,28,39 which may underlie the same expression pattern and subcellular targeting, these data strongly suggest that the localization and, thereby, the function of CB1 in the hippocampus is evolutionarily conserved. Interestingly, a strikingly similar localization of CB1 was recently shown in the retina of different vertebrate species as well.…”

Section: Similar Distribution Pattern Of Cb1 Cannabinoid Receptors Inmentioning

confidence: 70%

GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus

et al. 2000

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Abstract-Cannabinoids have been shown to disrupt memory processes in mammals including humans. Although the CB1 neuronal cannabinoid receptor was identified several years ago, neuronal network mechanisms mediating cannabinoid effects are still controversial in animals, and even more obscure in humans. In the present study, the localization of CB1 receptors was investigated at the cellular and subcellular levels in the human hippocampus, using control post mortem and epileptic lobectomy tissue. The latter tissue was also used for [ 3 H]GABA release experiments, testing the predictions of the anatomical data. Detectable expression of CB1 was confined to interneurons, most of which were found to be cholecystokinin-containing basket cells. CB1-positive cell bodies showed immunostaining in their perinuclear cytoplasm, but not in their somadendritic plasmamembrane. CB1-immunoreactive axon terminals densely covered the entire hippocampus, forming symmetrical synapses characteristic of GABAergic boutons. Human temporal lobectomy samples were used in the release experiments, as they were similar to the controls regarding cellular and subcellular distribution of CB1 receptors. We found that the CB1 receptor agonist, WIN 55,212-2, strongly reduced [ 3 H]GABA release, and this effect was fully prevented by the specific CB1 receptor antagonist SR 141716A.This unique expression pattern and the presynaptic modulation of GABA release suggests a conserved role for CB1 receptors in controlling inhibitory networks of the hippocampus that are responsible for the generation and maintenance of fast and slow oscillatory patterns. Therefore, a likely mechanism by which cannabinoids may impair memory and associational processes is an alteration of the fine-tuning of synchronized, rhythmic population events. ᭧ 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.Key words: CB1 receptor, cholecystokinin, presynaptic, synchronization, memory, release.Most behavioral effects of the active compound of marijuana and hashish are mediated by the CB1 cannabinoid receptor (CB1). 23 Although the impacts of cannabinoid-consumption on human and animal behaviour are well known, 1,3,7,43 the underlying physiological processes and the precise sites of cannabinoid actions in neural networks remain to be identified. The hippocampal formation is one of the brain areas with the highest level of CB1 receptor expression. 18,26,29 In accordance, at the behavioral level, cannabinoids typically interfere with hippocampal functions, i.e. they disrupt memory consolidation and associations both in humans and animals. 3,17 Although several recent experiments attempted to determine the mechanisms of cannabinoid action and the precise cellular and subcellular localization of the CB1 receptor in the rodent and primate hippocampus, the data they provide are inconsistent. 4,20,27,31,34,35,38,44,45 In the rodent hippocampus, a specific class of GABAergic interneurons was shown to express CB1 receptors. 20,27,45 Detailed electron microscopic investigation rev...

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Section: Similar Distribution Pattern Of Cb1 Cannabinoid Receptors Inmentioning

confidence: 70%

GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus

et al. 2000

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“…The psychotropic effects of D-9-THC are mediated by partial agonist effects at CB-1 receptors (CB-1R) where it has modest affinity (K i ¼ 35-80 nmol) and low intrinsic activity (Compton et al, 1992;Gerard et al, 1991;Howlett et al, 2002;Matsuda et al, 1990). However, its hydroxy metabolite has higher affinity and potency.…”

Section: The Mechanism Of the Psychotic Symptoms Induced By D-9-thcmentioning

confidence: 99%

The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis

D’Souza

Perry

MacDougall

et al. 2004

Neuropsychopharmacol

903

678

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Recent advances in the understanding of brain cannabinoid receptor function have renewed interest in the association between cannabinoid compounds and psychosis. In a 3-day, double-blind, randomized, and counterbalanced study, the behavioral, cognitive, and endocrine effects of 0, 2.5, and 5 mg intravenous delta-9-tetrahydrocannabinol (D-9-THC) were characterized in 22 healthy individuals, who had been exposed to cannabis but had never been diagnosed with a cannabis abuse disorder. Prospective safety data at 1, 3, and 6 months poststudy was also collected. D-9-THC (1) produced schizophrenia-like positive and negative symptoms; (2) altered perception; (3) increased anxiety; (4) produced euphoria; (5) disrupted immediate and delayed word recall, sparing recognition recall; (6) impaired performance on tests of distractibility, verbal fluency, and working memory (7) did not impair orientation; (8) increased plasma cortisol. These data indicate that D-9-THC produces a broad range of transient symptoms, behaviors, and cognitive deficits in healthy individuals that resemble some aspects of endogenous psychoses. These data warrant further study of whether brain cannabinoid receptor function contributes to the pathophysiology of psychotic disorders.

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“…4,15 CB1 cannabinoid receptors are widely expressed in the brain, 16 mainly in the neocortex, hippocampus, basal ganglia and cerebellum. 17 Cannabinoid receptors are codified by the CNR1 gene, located in chromosome 6q14-q15; 18 cDNA coding for CB1 was cloned by Gerard et al 19 in stem cells of the human brain. The sequence of human cannabinoid receptor contains 472 amino acids, it has seven transmembrane hydrophobic domains and it is a typical member of receptors coupled to G protein.…”

Section: Introductionmentioning

confidence: 99%

Depression in Parkinson's disease is related to a genetic polymorphism of the cannabinoid receptor gene (CNR1)

et al. 2005

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Depression is a common symptom in Parkinson's disease (PD) and it is present in up to 40% of the patients. The cause of depression in PD is thought to be related to disturbance of monoamine neurotransmission. The endogenous cannabinoid system mediates different brain processes that play a role in the control of behaviour and emotions. Cannabinoid function may be altered in neuropsychiatry diseases, directly or through interactions with monoamine, GABA and glutamate systems. For this reason, we have investigated whether there is a genetic risk factor for depression in PD linked to the polymorphisms of CB1 receptor gene. Depression was more frequent in patients with PD than in controls with osteoarthritis. The presence of depression did not correlate with the stage of the disease but it was more frequent in patients with pure akinetic syndrome than in those with tremoric or mixed type PD. The CB1 receptor gene polymorphism (AAT)n is considered to modify the transcription of the gene and, therefore, it may have functional relevance. We analysed the length of the polymorphic triplet (AAT)n of the gene that encodes CB1 (CNR1) receptor in 89 subjects (48 PD patients and 41 controls). In patients with PD, the presence of two long alleles, with more than 16 repeated AAT trinucleotides in the CNR1 gene, was associated with a reduced prevalence of depression (Fisher's exact test: P ¼ 0.003). This association did not reach significant differences in the control group, but the number of control individuals with depression was too small to allow for statistical analysis. Since the alleles with long expansions may have functional impact in cannabinoid neurotransmission, our data suggest that the pharmacological manipulation of cannabinoid neurotransmission could open a new therapeutic approach for the treatment of depression in PD and possibly in other conditions.

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Molecular cloning of a human cannabinoid receptor which is also expressed in testis

Cited by 623 publications

References 20 publications

GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus

GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus

The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis

Depression in Parkinson's disease is related to a genetic polymorphism of the cannabinoid receptor gene (CNR1)

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