Search results for " modulators"
showing 10 items of 97 documents
Differential diurnal variations of anandamide and 2-arachidonoyl-glycerol levels in rat brain.
2004
The endogenous ligands of cannabinoid receptors, also known as endocannabinoids, have been implicated in many physiological and pathological processes of the central nervous system. Here we show that the levels of the two major endocannabinoids, anandamide and 2-arachidonoyl-glycerol (2-AG), in four areas of the rat brain, change dramatically between the light and dark phases of the day. While anandamide levels in the nucleus accumbens, pre-frontal cortex, striatum and hippocampus were significantly higher in the dark phase, the opposite was observed with 2-AG, whose levels were significantly higher during the light phase in all four regions. We found that the activity of the fatty acid ami…
The effects of nitric oxide on striatal serotoninergic transmission involve multiple targets: an in vivo microdialysis study in the awake rat
2004
Abstract The role of endogenous nitric oxide (NO) in N -methyl- d -aspartate (NMDA)-induced modulation of serotonin (5-HT) release in the striatum of freely moving rats has been studied using microdialysis technique. NMDA-induced increase in 5-HT release was significantly inhibited by selective nitric oxide synthase (nNOS) inhibitor S -methylthiocitrulline (S-Me-TC), ONOO − scavenger l -cysteine ( l -cys), and guanylate cyclase (GC) inhibitor 1 H [1,2,4]oxadiazolo[4,3- a ]quinoxalin-1-one (ODQ). These data suggest that modulation of 5-HT levels is linked to the formation of NO produced by NMDA receptor activation and that endogenously produced NO increases 5-HT concentrations both by stimul…
Tackling Performance Challenges in Organic Photovoltaics: An Overview about Compatibilizers
2020
Organic Photovoltaics (OPVs) based on Bulk Heterojunction (BHJ) blends are a mature technology. Having started their intensive development two decades ago, their low cost, processability and flexibility rapidly funneled the interest of the scientific community, searching for new solutions to expand solar photovoltaics market and promote sustainable development. However, their robust implementation is hampered by some issues, concerning the choice of the donor/acceptor materials, the device thermal/photo-stability, and, last but not least, their morphology. Indeed, the morphological profile of BHJs has a strong impact over charge generation, collection, and recombination processes; control o…
Spinal Endocannabinoids and CB 1 Receptors Mediate C-Fiber–Induced Heterosynaptic Pain Sensitization
2009
Plastic Pain Perception Drugs and endocannabinoids acting on cannabinoid (CB) receptors have potential in the treatment of certain types of pain. In the spinal cord they are believed to suppress nociception, the perception of pain and noxious stimuli. Pernia-Andrade et al. (p. 760 ) now find that endocannabinoids, which are released in spinal cord by noxious stimulation, may promote rather than inhibit nociception by acting on CB1 receptors. Endocannabinoids not only depress transmission at excitatory synapses in the spinal cord, but also block the release of inhibitory neurotransmitters, thereby facilitating nociception.
The gamma(2)-MSH peptide mediates a central analgesic effect via a GABA-ergic mechanism that is independent from activation of melanocortin receptors.
2001
Using the latency for tail-flick after thermal stimulation we have assessed the effects of alpha-, gamma(1)- and gamma(2)-MSH on nociceptive threshold in the mice. Intracisternal injections of gamma(2)-MSH induced a distinct analgesia, while gamma(1)-MSH in the same doses gave only a minor analgesia. Intracisternal alpha-MSH instead gave a short-term hyperalgesia. The effect of gamma(2)-MSH was not blocked by any of the MC(4)/MC(3)receptor antagonist HS014, naloxone or by the prior intracisternal administrations of gamma(1)-MSH. However, the gamma(2)-MSH analgesic response was completely attenuated by treating animals with the GABA(A)antagonist bicuculline. The gamma(2)-MSH analgesic effect…
Synthesis and biological evaluation of 2-(3',4',5'-trimethoxybenzoyl)-3-N,N-dimethylamino benzo[b]furan derivatives as inhibitors of tubulin polymeri…
2008
Molecules that target microtubules have an important role in the treatment of cancer. A new class of inhibitors of tubulin polymerization based on the 2-(3,4,5-trimethoxybenzoyl)-2-dimethylamino-benzo[b]furan molecular skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. The most promising compound in this series was 2-(3,4,5-trimethoxybenzoyl)-3-dimethylamino-6-methoxy-benzo[b]furan, which inhibits cancer cell growth at nanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.
Synthesis and Biological Evaluation of 1-Methyl-2-(3',4',5'-trimethoxybenzoyl)-3-aminoindoles as a New Class of Antimitotic Agents and Tubulin Inhibi…
2008
The 2-(3,4,5-trimethoxybenzoyl)-2-aminoindole nucleus was used as the fundamental structure for the synthesis of compounds modified with respect to positions C-4 to C-7 with different moieties (chloro, methyl, or methoxy). Additional structural variations concerned the indole nitrogen, which was alkylated with small alkyl groups such as methyl or ethyl. We have identified 1-methyl-2-(3,4,5-trimethoxybenzoyl)-3-amino-7-methoxyindole as a new highly potent antiproliferative agent that targets tubulin at the colchicine binding site and leads to apoptotic cell death.
Involvement of CB1 and CB2 receptors in the modulation of cholinergic neurotransmission in mouse gastric preparations.
2007
Abstract While most of the studies concerning the role of cannabinoids on gastric motility have focused the attention on the gastric emptying in in vivo animal models, there is little information about the cannabinoid peripheral influence in the stomach. In addition, the functional features of CB2 receptors in the gastrointestinal tract have been poorly characterized. The purpose of the present study was to investigate the effects of cannabinoid drugs on the excitatory cholinergic and inhibitory non-adrenergic non-cholinergic (NANC) neurotransmission in mouse isolated gastric preparations. Intraluminal pressure from isolated whole stomach was recorded and mechanical responses induced by ele…
The endocannabinoid system controls key epileptogenic circuits in the hippocampus.
2006
SummaryBalanced control of neuronal activity is central in maintaining function and viability of neuronal circuits. The endocannabinoid system tightly controls neuronal excitability. Here, we show that endocannabinoids directly target hippocampal glutamatergic neurons to provide protection against acute epileptiform seizures in mice. Functional CB1 cannabinoid receptors are present on glutamatergic terminals of the hippocampal formation, colocalizing with vesicular glutamate transporter 1 (VGluT1). Conditional deletion of the CB1 gene either in cortical glutamatergic neurons or in forebrain GABAergic neurons, as well as virally induced deletion of the CB1 gene in the hippocampus, demonstrat…
Neuronal populations mediating the effects of endocannabinoids on stress and emotionality
2011
An adequate emotional response to stress is essential for survival and requires the fine-tuned regulation of several distinct neuronal circuits. Therefore, a precise control of these circuits is necessary to prevent behavioral imbalances. During the last decade, numerous investigations have evidenced that the endocannabinoid (eCB) system is able to crucially control stress coping. Its central component, the cannabinoid type 1 receptor (CB1 receptor), is located at the presynapse, where it is able to attenuate neurotransmitter release after its activation by postsynaptically produced and released eCBs. To date, the eCB system has been found to control the neurotransmitter release from severa…