Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of the synthetic cannabinoid receptor agonist WIN 55,212-2 on dopamine receptor-mediated alleviation of akinesia were evaluated in the reserpine-treated rat model of parkinsonism. The dopamine D2 receptor agonist quinpirole (0.1 mg/kg, ip) caused a significant alleviation of the akinesia. This effect was significantly reduced by coinjection with the cannabinoid receptor agonist WIN 55,212-2 (0.1 and 0.3 mg/kg). The simultaneous administration of the cannabinoid receptor antagonist SR 141716A (3 mg/kg, ip) with quinpirole and WIN 55,212-2 blocked the effect of WIN 55,212-2 on quinpirole-induced alleviation of akinesia. The selective dopamine D1 receptor agonist chloro-APB (SKF82958, 0.1 mg/kg) alleviated akinesia in a significant manner. WIN 55,212-2 (0.1-1 mg/kg, ip) did not affect the antiakinetic effect of chloro-APB. Combined injection of both D1 and D2 dopamine receptor agonists (both at either 0.1 or 0.02 mg/kg) resulted in a marked synergism of the antiakinetic effect. WIN 55,212-2 (0.1-1 mg/kg) significantly reduced the antiakinetic effect of combined injections of quinpirole and chloro-APB at both 0.1 and 0.02 mg/kg. The effect of 0.3 mg/kg WIN 55,212-2 on combined D1 and D2 agonist-induced locomotion (0.02 mg/kg) was blocked by SR 141761A (3 mg/kg). Neither WIN 55,212-2 alone (0.1 and 0.3 mg/kg) nor SR 141716A (3 and 30 mg/kg) alone had an antiparkinsonian effect. These results suggest that cannabinoids may modulate neurotransmission in the pathway linking the striatum indirectly to basal ganglia outputs via the lateral globus pallidus and the subthalamic nucleus.
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PMID:The cannabinoid receptor agonist WIN 55,212-2 reduces D2, but not D1, dopamine receptor-mediated alleviation of akinesia in the reserpine-treated rat model of Parkinson's disease. 939 68

We investigated interactions between cannabinoid and dopamine receptor systems in ICR mice. Mice were treated with the cannabinoid agonist levonantradol, the D(1) dopamine agonist 6-Br-APB, or the D(2) dopamine agonist quinelorane, or with combinations of these drugs. In addition, the D(1) antagonist SCH23390 was administered both alone and in combination with levonantradol. Two tests were used to evaluate changes in motor function: the immobility (ring stand) test and the catalepsy (bar) test. Levonantradol increased immobility and catalepsy in a dose-dependant manner. Both the D(2) agonist quinelorane and the D(1) agonist 6-Br-APB were able to attenuate the motor dysfunction caused by levonantradol. Administration of the D(1) antagonist SCH23390 enhanced the effects of levonantradol, producing a leftward shift of the log dose-response curve. These results differ from the augmentation by D(2) agonists of the hypoactivity induced by levonantradol in non-human primates [Meschler JP, Clarkson FA, Mathew PJ, Howlett AC, Madras BK. D(2), but not D(1) dopamine receptor agonists potentiate cannabinoid-induced sedation in nonhuman primates. J Pharmacol Exp Ther 2000;292:952-959], suggesting that conclusions about the interactions between the dopamine and cannabinoid receptor motor systems in rodents may not extend to primates.
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PMID:Cannabinoid and dopamine interaction in rodent brain: effects on locomotor activity. 1116 87

The present study was designed to determine the potential of CB1 cannabinoid receptor modulating compounds in the treatment of L-3,4-dihydroxyphenylalanine (L-dopa)-induced dyskinesia in Parkinson's disease. In the reserpine-treated rat model of parkinsonism, administration of a high dose of L-dopa (150 mg/kg) but not of Cl-APB (0.5 mg/kg) or quinpirole (0.5 mg/kg) produced a hyperkinetic state characterised by an increase in horizontal and vertical activity, which likely represent correlates of antiparkinsonian and dyskinetic activity, respectively. Injection of the CB1 cannabinoid receptor antagonist SR141716 (0.1-3 mg/kg) reduced the increase in vertical activity elicited by L-dopa without affecting the increase in horizontal activity. Injection of the CB1 cannabinoid receptor agonist WIN55,212-2 (0.1-3 mg/kg) reduced the L-dopa-induced increase in vertical activity and, at the highest dose only (3 mg/kg), also reduced horizontal activity elicited by L-dopa. WIN55,212-2 (1 mg/kg) reduced motor activity induced by both the D1 receptor agonist Cl-APB (0.5 mg/kg) and the D2 receptor agonist quinpirole (0.5 mg/kg) in the reserpine-treated rat. SR141716 (1 mg/kg) had no effects on motor activity induced by Cl-APB (0.5 mg/kg) nor quinpirole (0.5 mg/kg) in the reserpine-treated rat. Injection of the inhibitor of endocannabinoid transport AM404 (0.1-1 mg/kg) did not affect the increase in horizontal or vertical activity elicited by L-dopa (150 mg/kg) in the reserpine-treated rat. The data suggest that both CB1 cannabinoid receptor antagonists and agonists can modulate the behavioural effects of L-dopa and may be useful for the treatment of the dyskinesia associated with long-term L-dopa treatment of Parkinson's disease.
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PMID:Effects of CB1 cannabinoid receptor modulating compounds on the hyperkinesia induced by high-dose levodopa in the reserpine-treated rat model of Parkinson's disease. 1253 6

Although arachidonoyl ethanolamide (AEA or anandamide) is the first identified endocannabinoid, its roles in synaptic signaling and neuronal survival are still controversial. Here we report that AEA induced a dose-dependent elevation of the frequency of miniature excitatory postsynaptic currents (mEPSCs) in mouse hippocampal neurons in culture. This potentiation was not blocked by SR141716 or AM251, selective cannabinoid receptor antagonists, indicating that the AEA elevation of mEPSCs is not mediated via the CB1 receptor. Similarly, capsazepine and iodoresiniferatoxin, selective vanilloid receptor antagonists, and ryanodine also failed to inhibit the effect of AEA on mEPSCs. However, 2-APB and Xestospongin C, IP3 inhibitors, significantly attenuated AEA-induced increase in hippocampal excitatory synaptic transmission. Application of 3-deoxy-3-fluoro-d-myo-inositol 1,4,5-trisphosphate enhanced the frequency of mEPSCs and occluded the effect of AEA on mEPSCs. Our results suggest that AEA-produced stimulatory effect on excitatory glutamatergic synaptic transmission is likely mediated via an IP3 pathway.
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PMID:Anandamide potentiation of miniature spontaneous excitatory synaptic transmission is mediated via IP3 pathway. 2006 71

In rat paraventricular thalamic nucleus (PVT) neurons, activation of low-threshold calcium (Ca(2+)) channels triggers a low-threshold spike (LTS) which may be followed by slow afterpotentials that can dramatically influence action potential patterning. Using gluconate-based internal recording solutions, we investigated the properties of a LTS-induced slow afterdepolarization (sADP) observed in a subpopulation of PVT neurons recorded in brain slice preparations. This LTS-induced sADP required T-type Ca(2+) channel opening, exhibited variable magnitudes between neurons and a voltage dependency with a maximum near -50 mV. The area under the sADP remained stable during control monitoring, but displayed gradual suppression in media where strontium replaced Ca(2+). The sADP was suppressed following bath application of 2-APB or ML204, suggesting engagement of transient receptor potential canonical (TRPC)-like channels. Further investigation revealed a reversible suppression during bath applications of membrane permeable cannabinoid receptor (CBR) blockers rimonabant, AM630 or SR144528 suggesting the presence of both CB1Rs and CB2Rs. Similar results were achieved by intracellular, but not bath application of the membrane impermeant CB1R blocker hemopressin, suggesting an intracellular localization of CB1Rs. Data from pharmacologic manipulation of endocannabinoid biosynthetic pathways suggested 2-arachidonlyglycerol (2-AG) as the endogenous cannabinoid ligand, derived via hydrolysis of diacylglycerol (DAG), with the latter formed from the pathway involving phosphatidylcholine-specific phospholipase D and phosphatic acid phosphohydrolase. The sADP suppression observed during recordings with pipettes containing LY294002, a PI3-kinase inhibitor, suggested a role for PI3kinase in the translocation of these TRPC-like channels to the plasma membrane. Drug-induced attenuation of the availability of 2-AG influences the number of action potentials that surmount the LTS evoked in PVT neurons, implying an ongoing intracellular CBR modulation of neuronal excitability during LTS-induced bursting behavior.
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PMID:Endocannabinoid 2-AG and intracellular cannabinoid receptors modulate a low-threshold calcium spike-induced slow depolarizing afterpotential in rat thalamic paraventricular nucleus neurons. 2692 19