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

Systemically administered cannabinoids elicit marked cardiovascular effects, and the role of the central and the peripheral nervous system in these effects is not clarified. The aim of this study was to characterize the actions of cannabinoids on cardiovascular regulatory centers in conscious rabbits. A catheter for administration of drugs into the cisterna cerebellomedullaris and an electrode for recording renal sympathetic nerve activity were implanted under halothane anesthesia. Experiments were carried out later in conscious animals. Two cannabinoid receptor agonists were injected intracisternally: the aminoalkylindole WIN55212-2 (0.1, 1, and 10 microg kg(-1)) and the bicyclic Delta(9)-tetrahydrocannabinol analog CP55940 (0.1, 1, and 10 microg kg(-1)). WIN55212-2 and CP55940 dose dependently increased renal sympathetic nerve activity and the plasma noradrenaline concentration and also lowered the heart rate. The highest doses of WIN55212-2 and CP55940 increased blood pressure. In contrast, intracisternal injection of WIN55212-3 (0.1, 1, and 10 microg kg(-1)), an enantiomer of WIN55212-2 with very low affinity for cannabinoid binding sites, had no effects. The CB(1) cannabinoid receptor antagonist SR141716A (0.5 mg kg(-1), i.v. ) attenuated the effects of intracisternally administered WIN55212-2 (0.1, 1, and 10 microg kg(-1)). The results indicate that cannabinoids, acting directly on cardiovascular regulatory centers, elicit sympathoactivation and bradycardia. These effects were likely mediated by CB(1) cannabinoid receptors, because they were elicited by two cannabinoid agonists belonging to different chemical classes (WIN55212-2 and CP55940), but not by the inactive enantiomer WIN55212-3, and because they were attenuated by the CB(1) cannabinoid receptor antagonist SR141716A.
 ...
PMID:Cannabinoids cause central sympathoexcitation and bradycardia in rabbits. 1090 Feb 51

Cannabinoids produce antinociception via specific cannabinoid receptor activation, but there are also non-receptor mediated effects like for example the activation of the arachidonic acid cascade. Here we investigate the influence of cannabinoids (CB) on sleep duration after isoflurane anesthesia. We found that the CB receptor agonists R(-)-7-hydroxy-delta-6-tetra-hydrocannabinol-dimethylheptyl (HU-210) (0.1 mg/kg), 2-O-arachidonoylglycerylether (30 mg/kg) and arachidonyl-2-chloroethylamide (3 mg/kg) significantly prolong the duration of isoflurane induced sleep in mice (P<0.05). This effect was absent when co-injecting the selective CB(1) antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (1 mg/kg). Furthermore, HU-210 was ineffective in CB(1) receptor knockout mice (CB(1)-/-). Our behavioral tests (tail flick, rotarod) indicate that the sleep latency can be prolonged even at low drug dosages which do not influence thermal nociception. In the chosen dosages thimerosal (20 mg/kg), 2-AG (10 mg/kg), R(1)-methanandamide (R(1)-MAEA) (10 mg/kg) and flurbiprofen (27 mg/kg) were ineffective to increase sleep duration.
 ...
PMID:The cannabinoids R(-)-7-hydroxy-delta-6-tetra-hydrocannabinol-dimethylheptyl (HU-210), 2-O-arachidonoylglycerylether (HU-310) and arachidonyl-2-chloroethylamide (ACEA) increase isoflurane provoked sleep duration by activation of cannabinoids 1 (CB1)-receptors in mice. 1209 55

BOLD-contrast functional magnetic resonance imaging (fMRI) was used to investigate the effects of the synthetic cannabinoid agonist HU210 on the rat brain in order to determine potential CNS sites of action for the functional effects of cannabinoids. After obtaining basal data, rats (n=8) were given the cannabinoid agonist HU210 (10 microg/kg i.v.) and volume data sets collected for 85 mins. Significant increases in functional BOLD activity were observed in specific brain regions including those important in pain (PAG), reward (VTA and accumbens) and motor function (striatum). In order to confirm cannabinoid receptor involvement in the HU210 evoked functional BOLD activity, rats (n=8) were pre-treated with the CB1 cannabinoid receptor antagonist SR141716A (100 microg/kg i.v.) prior to HU210. Pretreatment with SR141716A abolished all significant evoked HU210 functional BOLD activity. To exclude the involvement of potential systemic effects induced by the cannabinoid agonist administration on the observed evoked functional BOLD activity a separate experiment investigated the effect of HU210 (10 microg/kg i.v.) on mean arterial pressure and showed that HU210 had no significant effect on pressure under chloral hydrate anaesthesia. In summary, this study demonstrates that the cannabinoid agonist HU210 evokes a significant increase in BOLD functional activity in specific regions and that this was cannabinoid receptor mediated. Furthermore the study indicates the potential value of fMRI in rodents to delineate pharmacologically induced changes in regional brain function.
 ...
PMID:Detection of cannabinoid agonist evoked increase in BOLD contrast in rats using functional magnetic resonance imaging. 1497 93

Cannabinoids have been shown to possess anticonvulsant properties in whole animal models of epilepsy. The present investigation sought to examine the effects of cannabinoid receptor activation on kainic acid (KA)-induced epileptiform neuronal excitability. Under urethane anesthesia, acute KA treatment (10 mg kg(-1), i.p.) entrained the spiking mode of simultaneously recorded neurons from random firing to synchronous bursting (% change in burst rate). Injection of the high-affinity cannabinoid agonist (-)-11-hydroxy-8-tetrahydrocannabinol-dimethyl-heptyl (HU210, 100 mug kg(-1), i.p.) following KA markedly reduced the burst frequency (% decrease in burst frequency) and reversed synchronized firing patterns back to baseline levels. Pre-treatment with the central cannabinoid receptor (CB1) antagonist N-piperidino-5-(4-clorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (rimonabant, SR141716A 3 mg kg(-1), i.p.) completely prevented the actions of HU210. The present results indicate that cannabinoids exert their antiepileptic effects by impeding pathological synchronization of neuronal networks in the hippocampus.
 ...
PMID:Cannabinoid receptor activation reverses kainate-induced synchronized population burst firing in rat hippocampus. 1956 87

The transient receptor potential vanilloid type 1 (TRPV1) channel is a well recognized polymodal signal detector that is activated by painful stimuli such as capsaicin. Here, we show that TRPV1 is expressed in the lateral nucleus of the amygdala (LA). Despite the fact that the central amygdala displays the highest neuronal density, the highest density of TRPV1 labeled neurons was found within the nuclei of the basolateral complex of the amygdala. Capsaicin specifically changed the magnitude of long-term potentiation (LTP) in the LA in brain slices of mice depending on the anesthetic (ether, isoflurane) used before euthanasia. After ether anesthesia, capsaicin had a suppressive effect on LA-LTP both in patch clamp and in extracellular recordings. The capsaicin-induced reduction of LTP was completely blocked by the nitric oxide synthase (NOS) inhibitor L-NAME and was absent in neuronal NOS as well as in TRPV1 deficient mice. The specific antagonist of cannabinoid receptor type 1 (CB1), AM 251, was also able to reduce the inhibitory effect of capsaicin on LA-LTP, suggesting that stimulation of TRPV1 provokes the generation of anandamide in the brain which seems to inhibit NO synthesis. After isoflurane anesthesia before euthanasia capsaicin caused a TRPV1-mediated increase in the magnitude of LA-LTP. Therefore, our results also indicate that the appropriate choice of the anesthetics used is an important consideration when brain plasticity and the action of endovanilloids will be evaluated. In summary, our results demonstrate that TRPV1 may be involved in the amygdala control of learning mechanisms.
 ...
PMID:Capsaicin-induced changes in LTP in the lateral amygdala are mediated by TRPV1. 2124 95

We report on seizures during anesthesia induction in animals treated with a cannabinoid receptor 1 (CB1R) antagonist for experimental sepsis. Animals received surgery for colon ascendens stent peritonitis-induced sepsis or sham surgery followed by treatment of CB1R antagonist, CB1R agonist, or placebo. Fourteen hours later, animals received pentobarbital or ketamine for anesthesia induction and animal behavior was observed. Tonic-clonic seizures were observed in 5 of 12 septic animals (42%) treated with CB1R antagonist after induction of anesthesia with pentobarbital. The data suggest that CB1R inhibition in combination with pentobarbital may increase the incidence of anesthetic-induced seizures in the case of sepsis.
 ...
PMID:Cannabinoid receptor 1 inhibition causes seizures during anesthesia induction in experimental sepsis. 2250 15