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Differential signalling in human cannabinoid CB1 receptors and their splice variants in autaptic hippocampal neurones.
Br J Pharmacol. 2012 Apr; 165(8):2660-71.BJ

Abstract

BACKGROUND AND PURPOSE

Cannabinoids such as Δ(9) - tetrahydrocannabinol, the major psychoactive component of marijuana and hashish, primarily act via cannabinoid CB(1) and CB(2) receptors to produce characteristic behavioural effects in humans. Due to the tractability of rodent models for electrophysiological and behavioural studies, most of the studies of cannabinoid receptor action have used rodent cannabinoid receptors. While CB(1) receptors are relatively well-conserved among mammals, human CB(1) (hCB(1)) differs from rCB(1) and mCB(1) receptors at 13 residues, which may result in differential signalling. In addition, two hCB(1) splice variants (hCB(1a) and hCB(1b)) have been reported, diverging in their amino-termini relative to hCB(1) receptors. In this study, we have examined hCB(1) signalling in neurones.

EXPERIMENTAL APPROACH

hCB(1) , hCB(1a) hCB(1b) or rCB(1) receptors were expressed in autaptic cultured hippocampal neurones from CB(1) (-/-) mice. Such cells express a complete endogenous cannabinoid signalling system. Electrophysiological techniques were used to assess CB(1) receptor-mediated signalling. KEY RESULTS Expressed in autaptic hippocampal neurones cultured from CB(1) (-/-) mice, hCB(1) , hCB(1a) and hCB(1b) signal differentially from one another and from rodent CB(1) receptors. Specifically, hCB(1) receptors inhibit synaptic transmission less effectively than rCB(1) receptors.

CONCLUSIONS AND IMPLICATIONS

Our results suggest that cannabinoid receptor signalling in humans is quantitatively very different from that in rodents. As the problems of marijuana and hashish abuse occur in humans, our results highlight the importance of studying hCB(1) receptors. They also suggest further study of the distribution and function of hCB(1) receptor splice variants, given their differential signalling and potential impact on human health.

LINKED ARTICLES

This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.

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Authors+Show Affiliations

Straiker A
Department of Psychological and Brain Sciences, Gill Center for Biomolecular Science, Indiana University, Bloomington, IN 47405, USA. straiker@indiana.edu
Wager-Miller J
No affiliation info available
Hutchens J
No affiliation info available
Mackie K
No affiliation info available

MeSH

Alternative SplicingAnimalsArachidonic AcidsCannabinoid Receptor ModulatorsDronabinolEndocannabinoidsExcitatory Postsynaptic PotentialsGlyceridesHEK293 CellsHippocampusHumansMiceMice, KnockoutNeuronsReceptor, Cannabinoid, CB1Signal Transduction

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22014238

Citation

Straiker, Alex, et al. "Differential Signalling in Human Cannabinoid CB1 Receptors and Their Splice Variants in Autaptic Hippocampal Neurones." British Journal of Pharmacology, vol. 165, no. 8, 2012, pp. 2660-71.
Straiker A, Wager-Miller J, Hutchens J, et al. Differential signalling in human cannabinoid CB1 receptors and their splice variants in autaptic hippocampal neurones. Br J Pharmacol. 2012;165(8):2660-71.
Straiker, A., Wager-Miller, J., Hutchens, J., & Mackie, K. (2012). Differential signalling in human cannabinoid CB1 receptors and their splice variants in autaptic hippocampal neurones. British Journal of Pharmacology, 165(8), 2660-71. https://doi.org/10.1111/j.1476-5381.2011.01744.x
Straiker A, et al. Differential Signalling in Human Cannabinoid CB1 Receptors and Their Splice Variants in Autaptic Hippocampal Neurones. Br J Pharmacol. 2012;165(8):2660-71. PubMed PMID: 22014238.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential signalling in human cannabinoid CB1 receptors and their splice variants in autaptic hippocampal neurones. AU - Straiker,Alex, AU - Wager-Miller,Jim, AU - Hutchens,Jacqueline, AU - Mackie,Ken, PY - 2011/10/22/entrez PY - 2011/10/22/pubmed PY - 2012/7/28/medline SP - 2660 EP - 71 JF - British journal of pharmacology JO - Br J Pharmacol VL - 165 IS - 8 N2 - BACKGROUND AND PURPOSE: Cannabinoids such as Δ(9) - tetrahydrocannabinol, the major psychoactive component of marijuana and hashish, primarily act via cannabinoid CB(1) and CB(2) receptors to produce characteristic behavioural effects in humans. Due to the tractability of rodent models for electrophysiological and behavioural studies, most of the studies of cannabinoid receptor action have used rodent cannabinoid receptors. While CB(1) receptors are relatively well-conserved among mammals, human CB(1) (hCB(1)) differs from rCB(1) and mCB(1) receptors at 13 residues, which may result in differential signalling. In addition, two hCB(1) splice variants (hCB(1a) and hCB(1b)) have been reported, diverging in their amino-termini relative to hCB(1) receptors. In this study, we have examined hCB(1) signalling in neurones. EXPERIMENTAL APPROACH: hCB(1) , hCB(1a) hCB(1b) or rCB(1) receptors were expressed in autaptic cultured hippocampal neurones from CB(1) (-/-) mice. Such cells express a complete endogenous cannabinoid signalling system. Electrophysiological techniques were used to assess CB(1) receptor-mediated signalling. KEY RESULTS Expressed in autaptic hippocampal neurones cultured from CB(1) (-/-) mice, hCB(1) , hCB(1a) and hCB(1b) signal differentially from one another and from rodent CB(1) receptors. Specifically, hCB(1) receptors inhibit synaptic transmission less effectively than rCB(1) receptors. CONCLUSIONS AND IMPLICATIONS: Our results suggest that cannabinoid receptor signalling in humans is quantitatively very different from that in rodents. As the problems of marijuana and hashish abuse occur in humans, our results highlight the importance of studying hCB(1) receptors. They also suggest further study of the distribution and function of hCB(1) receptor splice variants, given their differential signalling and potential impact on human health. LINKED ARTICLES: This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/22014238/Differential_signalling_in_human_cannabinoid_CB1_receptors_and_their_splice_variants_in_autaptic_hippocampal_neurones_ L2 - https://doi.org/10.1111/j.1476-5381.2011.01744.x DB - PRIME DP - Unbound Medicine ER -