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 cannabinoids on synaptic transmission were measured optically in rat hippocampal cultures. Synaptic release sites were labeled with the fluorescent dye FM1-43 in a stimulus-dependent manner. Action potential-induced release of FM1-43 required extracellular Ca2+ and was inhibited 65 +/- 3% by blockade of high-threshold voltage-gated Ca2+ channels with omega-grammotoxin SIA (300 nM). The cannabimimetic drug, Win 55212-2 (300 nM), inhibited FM1-43 release by 51 +/- 3%. The inhibition produced by Win55212-2 was blocked by the CB1 cannabinoid receptor antagonist, SR141716 (1 microM). The intensity of FM1-43 labeled puncta ranged 4-fold, although the inhibition produced by Win55212-2 was distributed normally across synaptic sites of various labeling intensities. The FM1-43-based optical method appears promising for the study of the effects of cannabinoids and other drugs on synaptic networks. These results indicate that cannabimimetics act presynaptically to inhibit the release of neurotransmitter and that this inhibition is observed uniformly at boutons of varied activity levels.
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PMID:Activation of CB1 cannabinoid receptors inhibits neurotransmitter release from identified synaptic sites in rat hippocampal cultures. 1067 67

The principal psychoactive ingredient in marijuana, Delta(9)-tetrahydrocannabinol, has been shown to inhibit adenylyl cyclase activity in vitro and can lead to impairment of memory in vivo. cAMP-induced changes in synaptic plasticity are thought to underlie memory formation. We examined the effects of cannabinoid receptor agonists on forskolin-induced formation of new synapses between rat hippocampal neurons in culture. Functional synaptic boutons were identified with FM1-43-based digital imaging. Cannabimimetic drugs prevented the recruitment of new synapses by inhibiting the formation of cAMP. The inhibition produced by Win55212-2, a synthetic cannabinoid receptor agonist, was stereoselective and was reversed by a selective CB1 receptor antagonist. Both Delta(9)-tetrahydrocannabinol and the endogenous ligand, anandamide, inhibited the formation of new synapses. Win55212-2 blocked the formation of new synapses induced by forskolin, but not those evoked by a membrane permeant cAMP analog. Thus, activation of cannabinoid receptors can modulate synaptic plasticity independent of direct effects on neurotransmitter release. Preventing the formation of new synapses may contribute to the impairment of memory produced by cannabinoids.
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PMID:Cannabinoids inhibit the formation of new synapses between hippocampal neurons in culture. 1131 44