Meta-analysis of cannabinoid ligand binding affinity and receptor distribution

interspecies differences

J. M. McPartland, M. Glass, R. G. Pertwee

Research output: Contribution to journalLiterature review

123 Citations (Scopus)

Abstract

A meta-analysis, unlike a literature review, synthesizes previous studies into new results. Pooled data from 211 studies measured ligand binding affinities at human (Hs) or rat (Rn) cannabinoid receptors CB1 and CB2. Cochrane methods were modified for this non-clinical analysis. Meta-regression detected data heterogeneity arising from methodological factors: use of sectioned tissues, lack of PMSF and choice of radioligand. Native brain tissues exhibited greater affinity (lower nM) than transfected cells, but the trend fell short of significance, as did the trend between centrifugation and filtration methods. Correcting for heterogeneity, mean K-i values for Delta(9)-tetrahydrocannabinol differed significantly between HsCB(1) and RnCB1 (25.1 and 42.6 nM, respectively) but not between HsCB1 and HsCB(2) (25.1 and 35.2). Mean K-d values for HsCB(1), RnCB1 and HsCB(2) of CP55,940 (2.5, 0.98, 0.92) and WIN55,212-2 (16.7, 2.4, 3.7) differed between HsCB(1) and RnCB1 and between HsCB(1) and HsCB(2). SR141716A differed between HsCB(1) and RnCB1 (2.9 and 1.0 nM). Anandamide at HsCB(1), RnCB1 and HsCB(2) (239.2, 87.7, 439.5) fell short of statistical differences due to heterogeneity. We consider these Kd and Ki values to be the most valid estimates in the literature. Sensitivity analyses did not support the numerical validity of cannabidiol, cannabinol, 2-arachidonoyl glycerol and all ligands at RnCB2. Aggregate rank order analysis of CB1 distribution in the brain (pooled from 119 autoradiographic, immunohistochemical and in situ hybridization studies) showed denser HsCB(1) expression in cognitive regions (cerebral cortex) compared to RnCB1, which was relatively richer in movement-associated areas (cerebellum, caudateputamen). Implications of interspecies differences are discussed.

Original languageEnglish
Pages (from-to)583-593
Number of pages11
JournalBritish Journal of Pharmacology
Volume152
Issue number5
Early online date16 Jul 2007
DOIs
Publication statusPublished - Nov 2007

Keywords

  • anandamide
  • cannabinoid
  • cannabis
  • directed molecular evolution
  • endocannabinoid
  • meta-analysis
  • pharmacogenetics
  • species specificity
  • structure-activity relationship
  • tetrahydrocannabinol
  • rat-brain
  • signal-transduction
  • CB2 receptors
  • species-differences
  • terminal tail
  • delta-9-tetrahydrocannabinol
  • localization
  • agonists
  • long
  • antagonist

Cite this

Meta-analysis of cannabinoid ligand binding affinity and receptor distribution : interspecies differences. / McPartland, J. M.; Glass, M.; Pertwee, R. G.

In: British Journal of Pharmacology, Vol. 152, No. 5, 11.2007, p. 583-593.

Research output: Contribution to journalLiterature review

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AU - Glass, M.

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N2 - A meta-analysis, unlike a literature review, synthesizes previous studies into new results. Pooled data from 211 studies measured ligand binding affinities at human (Hs) or rat (Rn) cannabinoid receptors CB1 and CB2. Cochrane methods were modified for this non-clinical analysis. Meta-regression detected data heterogeneity arising from methodological factors: use of sectioned tissues, lack of PMSF and choice of radioligand. Native brain tissues exhibited greater affinity (lower nM) than transfected cells, but the trend fell short of significance, as did the trend between centrifugation and filtration methods. Correcting for heterogeneity, mean K-i values for Delta(9)-tetrahydrocannabinol differed significantly between HsCB(1) and RnCB1 (25.1 and 42.6 nM, respectively) but not between HsCB1 and HsCB(2) (25.1 and 35.2). Mean K-d values for HsCB(1), RnCB1 and HsCB(2) of CP55,940 (2.5, 0.98, 0.92) and WIN55,212-2 (16.7, 2.4, 3.7) differed between HsCB(1) and RnCB1 and between HsCB(1) and HsCB(2). SR141716A differed between HsCB(1) and RnCB1 (2.9 and 1.0 nM). Anandamide at HsCB(1), RnCB1 and HsCB(2) (239.2, 87.7, 439.5) fell short of statistical differences due to heterogeneity. We consider these Kd and Ki values to be the most valid estimates in the literature. Sensitivity analyses did not support the numerical validity of cannabidiol, cannabinol, 2-arachidonoyl glycerol and all ligands at RnCB2. Aggregate rank order analysis of CB1 distribution in the brain (pooled from 119 autoradiographic, immunohistochemical and in situ hybridization studies) showed denser HsCB(1) expression in cognitive regions (cerebral cortex) compared to RnCB1, which was relatively richer in movement-associated areas (cerebellum, caudateputamen). Implications of interspecies differences are discussed.

AB - A meta-analysis, unlike a literature review, synthesizes previous studies into new results. Pooled data from 211 studies measured ligand binding affinities at human (Hs) or rat (Rn) cannabinoid receptors CB1 and CB2. Cochrane methods were modified for this non-clinical analysis. Meta-regression detected data heterogeneity arising from methodological factors: use of sectioned tissues, lack of PMSF and choice of radioligand. Native brain tissues exhibited greater affinity (lower nM) than transfected cells, but the trend fell short of significance, as did the trend between centrifugation and filtration methods. Correcting for heterogeneity, mean K-i values for Delta(9)-tetrahydrocannabinol differed significantly between HsCB(1) and RnCB1 (25.1 and 42.6 nM, respectively) but not between HsCB1 and HsCB(2) (25.1 and 35.2). Mean K-d values for HsCB(1), RnCB1 and HsCB(2) of CP55,940 (2.5, 0.98, 0.92) and WIN55,212-2 (16.7, 2.4, 3.7) differed between HsCB(1) and RnCB1 and between HsCB(1) and HsCB(2). SR141716A differed between HsCB(1) and RnCB1 (2.9 and 1.0 nM). Anandamide at HsCB(1), RnCB1 and HsCB(2) (239.2, 87.7, 439.5) fell short of statistical differences due to heterogeneity. We consider these Kd and Ki values to be the most valid estimates in the literature. Sensitivity analyses did not support the numerical validity of cannabidiol, cannabinol, 2-arachidonoyl glycerol and all ligands at RnCB2. Aggregate rank order analysis of CB1 distribution in the brain (pooled from 119 autoradiographic, immunohistochemical and in situ hybridization studies) showed denser HsCB(1) expression in cognitive regions (cerebral cortex) compared to RnCB1, which was relatively richer in movement-associated areas (cerebellum, caudateputamen). Implications of interspecies differences are discussed.

KW - anandamide

KW - cannabinoid

KW - cannabis

KW - directed molecular evolution

KW - endocannabinoid

KW - meta-analysis

KW - pharmacogenetics

KW - species specificity

KW - structure-activity relationship

KW - tetrahydrocannabinol

KW - rat-brain

KW - signal-transduction

KW - CB2 receptors

KW - species-differences

KW - terminal tail

KW - delta-9-tetrahydrocannabinol

KW - localization

KW - agonists

KW - long

KW - antagonist

U2 - 10.1038/sj.bjp.0707399

DO - 10.1038/sj.bjp.0707399

M3 - Literature review

VL - 152

SP - 583

EP - 593

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

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ER -