Effect of phenylmethylsulphonyl fluoride on the potency of anandamide as an inhibitor of electrically evoked contractions in two isolated tissue preparations

Pertwee, Roger G.; Fernando, Susanthi R.; Griffin, Graeme; Abadji, Vasiliki; Makriyannis, Alexandros

doi:10.1016/0014-2999(94)00618-h

Cited by 75 publications

(53 citation statements)

References 9 publications

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“…Release-modulating CB1 receptors have not only been identified in the autonomic nervous system (Pertwee et al 1993(Pertwee et al , 1995(Pertwee et al , 1996Howlett 1995) but, very recently, also in slices (Gifford and Ashby 1996) and cultured cells from the rat hippocampus (Shen et al 1996). They may represent a new type of presynaptic receptor.…”

Section: Discussionmentioning

confidence: 99%

“…The CB1 receptor is G protein-coupled and its activation causes inhibition of adenylyl cyclase and blockade of Ca 2+ channels (see Howlett 1995). By means of several potent agonists belonging to different chemical classes (for review see Howlett 1995) and a potent and selective antagonist, SR 141716 (Rinaldi-Carmona et al 1994, 1995, inhibitory presynaptic CB1 receptors have been identified in the autonomic nerves of the mouse vas deferens and in the guinea-pig myenteric plexus (Pertwee et al 1993(Pertwee et al , 1995(Pertwee et al , 1996Howlett 1995). The aim of the present study was to examine the effect of cannabinoid receptor ligands on neurotransmitter release from dopaminergic neurones of the guinea-pig retina, which is used as a model of the CNS (for review, see Nowak 1988).…”

Section: Introductionmentioning

confidence: 99%

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Cannabinoid receptor-mediated inhibition of dopamine release in the retina

Schlicker

Timm

Göthert

1996

Naunyn-Schmiedeberg's Arch Pharmacol

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The possible occurrence of cannabinoid (CB) receptors was studied on superfused guinea-pig retinal discs preincubated with [3H]dopamine or [3H]noradrenaline. Tritium overflow was evoked either electrically (3 Hz) or by re-introduction of Ca2+ 1.3 mM after superfusion with Ca(2+)-free medium containing K+ 30 mM. The accumulation of [3H]dopamine ([3H]DA) and [3H]noradrenaline ([3H]NA) was inhibited by the selective inhibitor of the neuronal dopamine transporter GBR-12909 (pIC50% 7.29 and 7.41, respectively) but not by the selective inhibitor of the neuronal noradrenaline transporter desipramine (1 microM). The electrically or Ca(2+)-evoked tritium overflow in retinal discs preincubated with [3H]DA or [3H]NA was reduced by the CB receptor agonists CP-55,940 and WIN 55,212-2 (pIC50% in discs preincubated with [3H]NA, electrical stimulation: 7.03 and 6.70, respectively) but not affected by the inactive S(-)enantiomer of the latter, WIN 55,212-3 (up to 10 microM). The concentration-response curve of WIN 55,212-2 was shifted to the right by the CB1 receptor antagonist SR 141716 (apparent pA2: 8.29) which, by itself, increased the evoked overflow. The facilitatory effect of SR 141716 was not affected by GBR-12909 and the dopamine receptor antagonist haloperidol. In conclusion, the dopaminergic neurones of the guinea-pig retina can be labelled by both [3H]DA and [3H]NA. Transmitter release from the dopaminergic neurones is inhibited by activation of cannabinoid receptors of the CB1 type, which appear to be tonically activated by an endogenous CB receptor ligand.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cannabinoid receptor-mediated inhibition of dopamine release in the retina

Schlicker

Timm

Göthert

1996

Naunyn-Schmiedeberg's Arch Pharmacol

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“…A functional role for endocannabinoids and CB 1 receptors in the gastrointestinal tract is supported by pharmacological studies demonstrating that anandamide and various CB 1 agonists (WIN 55,212-2, CP55,940, and ACEA) but not the CB 2 -selective agonists JWH-133 inhibit gastrointestinal motility in rodents in vivo and in isolated ileum and colon from both experimental animals and humans (Shook and Burks, 1989;Pertwee et al, 1995Pertwee et al, , 1996Coutts and Pertwee, 1997;McCallum et al, 1999;Mancinelli et al, 2001;Mang et al, 2001;Landi et al, 2002;Manara et al, 2002;Hinds et al, 2006). A similar role for endogenous substrates of FAAH is suggested by recent in vivo findings in mice, documenting inhibition of intestinal motility by the FAAH inhibitors N-arachidonoylserotonin and palmitoylisopropylamide and by the FAAH substrates palmitoylethanolamide, oleamide, and oleoylethanolamide in wildtype but not in FAAH knockout mice (Capasso et al, 2005).…”

Section: G Gastrointestinal and Liver Disordersmentioning

confidence: 99%

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

2006

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“…Cell pellets were resuspended and incubated on ice for 30 min in homogenization buffer (10 mM Tris-HCl, 5 mM EDTA, 3 mM EGTA, pH 7.6) containing 1 mM phenylmethylsulfonyl fluoride as a protease and amidase inhibitor (13,14). Cells were then homogenized with 15-20 strokes at 900 rpm with a Dounce homogenizer using stirrer type RZR1 polytron homogenizer (Caframo, Wiarton, Ontario).…”

Section: Methodsmentioning

confidence: 99%

Characterization of Peripheral Human Cannabinoid Receptor (hCB2) Expression and Pharmacology Using a Novel Radioligand, [35S]Sch225336

Gonsiorek¹,

Hesk²,

Chen³

et al. 2006

Journal of Biological Chemistry

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Studies to characterize the endogenous expression and pharmacology of peripheral human cannabinoid receptor (hCB2) have been hampered by the dearth of authentic anti-hCB2 antibodies and the lack of radioligands with CB2 selectivity. We recently described a novel CB2 inverse agonist, The endocannabinoids, anandamide and 2-arachidonyl glycerol, are ligands for two G protein-coupled cannabinoid receptors, CB1 2 and CB2. It has been hypothesized that human CB2 (hCB2) and its ligands are immune regulators due to the defined expression of hCB2 mRNA in peripheral immune cells and tissues. This hypothesis was bolstered by studies showing that 2-arachidonyl glycerol, a full agonist at hCB2 (1), stimulated chemotaxis of various hemopoietic cells, including differentiated monocytic and eosinophilic cells such as HL-60, THP-1, U937, and leukemia EoL-1 cells as well as human monocytes, eosinophils, and dendritic cells (2-4). CB2 was implicated in this response due to its sensitivity to blockade by the CB2 inverse agonist, SR144528. However, direct measurement of hCB2 protein expression in immune cells has been hampered by the lack of radioligands with CB2 selectivity and high specific activity. Binding analyses of CB2 have used tritiated agonists such as [ 3 H]CP55,940 or [ 3 H]WIN55,212 that bind with low nanomolar affinity but have low specific activities (specific activity, 20 -180 Ci/mmol) and little or no selectivity versus CB1. As a result, CB2 pharmacology has been almost completely restricted to studies with recombinantly expressed receptor (for review, see Ref. 5). Recently, we described a novel CB2 inverse agonist, S]Sch225336, a highly potent and CB2-selective radioligand with high specific activity (Ͼ1400 Ci/mmol). The studies presented herein describe the use of this unique radioligand to extensively characterize CB2 expressed endogenously in blood cells, cell lines, and tissue sections.

show abstract

Effect of phenylmethylsulphonyl fluoride on the potency of anandamide as an inhibitor of electrically evoked contractions in two isolated tissue preparations

Cited by 75 publications

References 9 publications

Cannabinoid receptor-mediated inhibition of dopamine release in the retina

Cannabinoid receptor-mediated inhibition of dopamine release in the retina

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

Characterization of Peripheral Human Cannabinoid Receptor (hCB2) Expression and Pharmacology Using a Novel Radioligand, [35S]Sch225336

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