Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice

Zimmer, Andreas; Zimmer, Anne; Hohmann, Andrea G.; Herkenham, Miles; Bonner, Tom I.

doi:10.1073/pnas.96.10.5780

Cited by 957 publications

(750 citation statements)

References 44 publications

Supporting

Mentioning

695

Contrasting

Unclassified

Order By: Relevance

“…Since the major brain cannabinoid receptor is CB 1 , and the specificity of SR141716A as a pure CB 1 antagonist is controversial, we decided to use the CB 1 knockout mice to study the role of CB 1 receptor in neuroprotection. As reported by Zimmer et al (1999), we also found that the naive CB 1 (À/À) mice display some motor deficits, unrelated to the trauma. As expected, after injury, their spontaneous recovery was extremely slow, as compared with the WT mice, suggesting that the endogenous cannabinoids play a role in the spontaneous recovery after CHI.…”

Section: Discussionsupporting

confidence: 88%

CB₁ cannabinoid receptors are involved in neuroprotection via NF-κB inhibition

Panikashvili

Mechoulam

Beni

et al. 2005

J Cereb Blood Flow Metab

164

144

View full text Add to dashboard Cite

We reported earlier that closed head injury (CHI) in mice causes a sharp elevation of brain 2-arachidonoylglycerol (2-AG) levels, and that exogenous 2-AG reduces brain edema, infarct volume and hippocampal death and improved clinical recovery after CHI. The beneficial effect of 2-AG was attenuated by SR141716A, a CB 1 cannabinoid receptor antagonist, albeit at relatively high doses. In the present study, we further explored the role of CB 1 receptors in mediating 2-AG neuroprotection. CB 1 receptor knockout mice (CB 1 (À/À)) showed minor spontaneous recovery at 24 h after CHI, in contrast to the significant improvement in neurobehavioral function seen in wild-type (WT) mice. Moreover, administration of 2-AG did not improve neurological performance and edema formation in the CB 1 (À/À) mice. In addition, 2-AG abolished the three-to four-fold increase of nuclear factor jB (NF-jB) transactivation, at 24 h after CHI in the WT mice, while it had no effect on NF-jB in the CB 1 (À/À) mice, which was as high as in the WT vehicle-treated mice. We thus propose that 2-AG exerts its neuroprotection after CHI, at least in part, via CB 1 receptor-mediated mechanisms that involve inhibition of intracellular inflammatory signaling pathways.

show abstract

Section: Discussionsupporting

confidence: 88%

CB₁ cannabinoid receptors are involved in neuroprotection via NF-κB inhibition

Panikashvili

Mechoulam

Beni

et al. 2005

J Cereb Blood Flow Metab

164

144

View full text Add to dashboard Cite

show abstract

“…CP55940 interacts with GPR55 at a potency 25-fold lower than at CB 1 in the comparable experimental system used here. [ 3 H]-CP55940 has been used in several studies (Zimmer et al, 1999;Buckley et al, 2000) to examine cannabinoid receptor distribution. Because GPR55 binds the radioligand [ 3 H]-CP55940 it may be expected that this radioligand would detect the presence of GPR55, especially in CB 1 and CB 2 knockout mice, but this has not been the case (Zimmer et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

The orphan receptor GPR55 is a novel cannabinoid receptor

Ryberg

Larsson

Sjögren

et al. 2007

British J Pharmacology

1,341

1,451

View full text Add to dashboard Cite

Background: The endocannabinoid system functions through two well characterized receptor systems, the CB 1 and CB 2 receptors. Work by a number of groups in recent years has provided evidence that the system is more complicated and additional receptor types should exist to explain ligand activity in a number of physiological processes. Experimental approach: Cells transfected with the human cDNA for GPR55 were tested for their ability to bind and to mediate GTPgS binding by cannabinoid ligands. Using an antibody and peptide blocking approach, the nature of the Gprotein coupling was determined and further demonstrated by measuring activity of downstream signalling pathways.Key results: We demonstrate that GPR55 binds to and is activated by the cannabinoid ligand CP55940. In addition endocannabinoids including anandamide and virodhamine activate GTPgS binding via GPR55 with nM potencies. Ligands such as cannabidiol and abnormal cannabidiol which exhibit no CB 1 or CB 2 activity and are believed to function at a novel cannabinoid receptor, also showed activity at GPR55. GPR55 couples to Ga13 and can mediate activation of rhoA, cdc42 and rac1. Conclusions: These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB 1 and CB 2 described here will permit delineation of its physiological function(s).

show abstract

“…Experiments were carried out on male Wistar rats weighing 150-170 g received from the breeding colony of Semmelweis University and on CB1 receptor knockout (-/-, CB 1 R KO) and wild type (+/+, WT) C57BL/6J mice (21-25 g), kindly provided by Professor Andreas Zimmer, University of Bonn (Zimmer et al, 1999).…”

Section: Animalsmentioning

confidence: 99%

Angiotensin II-induced activation of central AT1 receptors exerts endocannabinoid-mediated gastroprotective effect in rats

Gyires

Rónai

Zádori

et al. 2014

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

The aim of the present study was to analyze whether angiotensin II via the endocannabinoid system can induce gastric mucosal protection, since transactivation of cannabinoid CB1 receptors by angiotensin AT1 receptor in CHO cells was described. Experimental ulcer was induced by acidified ethanol given orally in male Wistar rats, CB1(+/+) wild type and CB1(-/-) knock out mice. The compounds were administered intracerebroventricularly. It was found, that 1./ Angiotensin II inhibited the ethanol-induced gastric lesions (11.9-191 pmol); the effect of angiotensin II (191 pmol) was inhibited by the CB1 receptor inverse agonist AM 251 (1.8 nmol) and the inhibitor of diacylglycerol lipase (DAGL), tetrahydrolipstatin (0.2 nmol). 2./ Angiotensin II exerted gastroprotection in wild type, but not in CB1(-/-) mice. 3./ The gastroprotective effect of angiotensin II (191 pmol) was reduced by atropine (1 mg/kg i.v.) and bilateral cervical vagotomy. In conclusion, stimulation of central angiotensin AT1 receptors via activation of cannabinoid CB1 receptors induces gastroprotection in a DAGL-dependent and vagus-mediated mechanism.

show abstract

Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice

Cited by 957 publications

References 44 publications

CB₁ cannabinoid receptors are involved in neuroprotection via NF-κB inhibition

CB₁ cannabinoid receptors are involved in neuroprotection via NF-κB inhibition

The orphan receptor GPR55 is a novel cannabinoid receptor

Angiotensin II-induced activation of central AT1 receptors exerts endocannabinoid-mediated gastroprotective effect in rats

Contact Info

Product

Resources

About

Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice

Cited by 957 publications

References 44 publications

CB1 cannabinoid receptors are involved in neuroprotection via NF-κB inhibition

CB1 cannabinoid receptors are involved in neuroprotection via NF-κB inhibition

The orphan receptor GPR55 is a novel cannabinoid receptor

Angiotensin II-induced activation of central AT1 receptors exerts endocannabinoid-mediated gastroprotective effect in rats

Contact Info

Product

Resources

About

CB₁ cannabinoid receptors are involved in neuroprotection via NF-κB inhibition

CB₁ cannabinoid receptors are involved in neuroprotection via NF-κB inhibition