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Control of the Upper Airway during Sleep
Published in Susmita Chowdhuri, M Safwan Badr, James A Rowley, Control of Breathing during Sleep, 2022
Suppression of motoneuronal excitability caused by a reduced release (withdrawal) of 5-HT, NE, ORX, TRH, and substance P occurs through the opening of potassium ion (K+) channels (136, 137). The considerable molecular diversity of these channels makes them potentially attractive targets for pharmacological interventions that aim to increase upper airway muscle tone during sleep. Recently, Grace et al. (67) investigated the effects of microdialysis perfusion of the XII nucleus region with various K+ channel blockers in chronically instrumented, behaving rats. Their main observations were that: (a) perfusion with a solution containing barium ions (blockers of inwardly rectifying K+ channels) elevated tongue EMG in all sleep-wake states, with the effect being most prominent during wakefulness and REM sleep with muscle twitches; (b) perfusion with methanandamide (antagonist of the tandem pore domain (TASK) channels) produced activation limited to wakefulness; and (c) perfusion with either 4-aminopyridine or tetraethylammonium (blockers of different voltage-dependent K+ channels) increased GG activity across all sleep-wake states but most prominently during REM sleep with twitches. Collectively, closure of certain K+ channels elevated tongue EMG during sleep to the levels comparable to those during wakefulness. In normal rats, the effects mediated by TASK channels appear detectable during wakefulness only (138), but following exposure to chronic intermittent hypoxia (CIH), at least TASK-1 channels are upregulated in the XII nucleus (139).
The function of the endocannabinoid system in the pancreatic islet and its implications on metabolic syndrome and diabetes
Published in Islets, 2023
Edgardo Cortes-Justo, Sergio H Garfias-Ramírez, Alonso Vilches-Flores
The development of pharmacological analogs and agonists, first for CB1 receptor and then for CB2 receptor, has been a useful in the study of mechanisms of action, binding and biological effects.1,2,5,45,51,52,56–58 CB1 receptor agonist methanandamide increased intracellular Ca2+ oscillations in 31.3% of the beta-cells tested (10 out of 32), similarly to the secondary effect of AEA.37 Selective agonists for CB1 receptor, arachidonyl cyclopropylamine (ACPA) and arachidonyl-2-chloroethylamine (ACEA), as well as JWH-015 for CB2 receptor, have been usually studied in isolated islets from animal models and humans.43,50–52,56–59 At short exposure, ACEA increases the release of intracellular Ca2+ by activating the phosphatidyl-inositol-triphosphate (IP3) receptor in the endoplasmic reticulum, however the effect on insulin secretion is not clear since some studies demonstrate an inhibition, while others propose a significant increase of basal secretion.51,58 Isolated islets from mice and human chronically exposed to ACEA induced an adaptable ECS response, probably involving a process of saturation and self-regulation of receptors’ expression, meanwhile acute exposition decreased insulin secretion and apoptosis.51,52,56 Acute and chronic effects of JWH-015 were most evident in alpha-cells, evoking increase in glucagon secretion, content, and gene expression.51,52
Cannabis as a potential compound against various malignancies, legal aspects, advancement by exploiting nanotechnology and clinical trials
Published in Journal of Drug Targeting, 2022
Nazeer Hasan, Mohammad Imran, Afsana Sheikh, Suma Saad, Gaurav Chaudhary, Gaurav Kumar Jain, Prashant Kesharwani, Farhan J. Ahmad
Prostate tumour is the second most occurring among the most invasive carcinoma so far. An elevated level of CB-1 and CB-2 were observed in prostate tissues and a variety of cells lines: DU-145, LNCaP, PC-3, and CWR22Rv1 [118,119]. Cannabinoid agonist, JWH-015, stimulated ceramide release through de novo synthesis that triggered cell death following inhibition of the Akt pathway while activating the JNK pathway [120]. Anamide, a psychoactive agonist of cannabis, promoted the antitumor efficacy via accumulation of ceramide with downregulation of epidermal growth factor receptor (EGFR). The (R)-methanandamide, a CB-1 receptor agonist, the profoundly established anti-metastatic effect at a very low dose after treatment with LNCaP cell [121]. Induction of apoptosis was witnessed in PC-3 cells due to activation of cannabinoid receptor-mediated by Δ9–THC that further activated the PI3K/Akt pathway [122]. Cannabinoids could successfully down-regulate the expression of pro-inflammatory cytokines, prostate-specific antigen, and vascular endothelial growth factor (VEGF). The team reported a reduction in prostate-specific antigen secretion (PSA) and PSA mRNA expression, illustrating the importance of cannabis in the prevention of prostate cancer progression [123].
Targeting the endocannabinoid system as a potential anticancer approach
Published in Drug Metabolism Reviews, 2018
Rico Schwarz, Robert Ramer, Burkhard Hinz
In addition, stable analogs of AEA were found to confer inhibition of cancer cell growth and spread. As such, arachidonoyl-2′-chloroethylamide (ACEA) revealed antiproliferative properties on colorectal carcinoma cells (Ligresti et al. 2003). Moreover, R(+)-methanandamide was demonstrated to induce apoptosis in cervical and lung cancer cell lines (Eichele et al. 2009) and glioma cells (Hinz et al. 2004a; Eichele et al. 2006). Notably, these proapoptotic effects of R(+)-methanandamide on cervical cancer (Eichele et al. 2009) and glioma cells (Hinz et al. 2004a) were not sensitive toward antagonists of cannabinoid receptors as well as TRPV1. On the contrary, R(+)-methanandamide-induced apoptosis of mantle cell lymphoma cells was found to depend on activation of both CB1 and CB2 receptors (Gustafsson et al. 2006). A recent study was further able to demonstrate AEA as well as R(+)-methanandamide to confer a proapoptotic action on prostate cancer cells via CB1 (Orellana-Serradell et al. 2015).