Neuromuscular junction (NMJ) induces a biphasic modulation of evoked neurotransmitter release: an initial depression followed by a delayed enhancement. The depression is mediated by the release from the endocannabinoid 2-arachidonylglycerol (2-AG) in the muscle and its binding to cannabinoid sort 1 receptors on the motor nerve terminal. The function presented right here suggests that the delayed enhancement of neurotransmitter release is mediated by cyclooxygenase-2 (COX-2) since it converts 2-AG to the glycerol ester of prostaglandin E2 (PGE2 -G). Utilizing immunofluorescence, COX-2 was detected in the perisynaptic Schwann cells (PSCs) surrounding the NMJ. Pretreatment with either with the selective COX-2 inhibitors, nimesulide or DuP 697, prevents the delayed boost in endplate prospective (EPP) amplitude normally produced by muscarine. In keeping with its putative function as a mediator in the delayed muscarinic effect, PGE2 -G enhances evoked neurotransmitter release. Particularly, PGE2 -G increases the amplitude of EPPs without having altering that of spontaneous miniature EPPs. As shown previously for the muscarinic effect, the enhancement of evoked neurotransmitter release by PGE2 -G depends upon nitric oxide (NO) because the response is abolished by application of either N G -nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, or carboxy-PTIO, a chelator of NO.N-Fmoc-3-iodo-L-alanine methyl ester Chemical name Intriguingly, the enhancement is not prevented by AH6809, a prostaglandin receptor antagonist, but is blocked by capsazepine, a TRPV1 and TRPM8 receptor antagonist. Taken with each other, these outcomes suggestC2013 The Authors. The Journal of PhysiologyC2013 The Physiological SocietyDOI: 10.1113/jphysiol.2013.C. Lindgren and othersJ Physiol 591.that the conversion of 2-AG to PGE2 -G by COX-2 underlies the muscarine-induced enhancement of neurotransmitter release in the vertebrate NMJ.(Received 9 April 2013; accepted following revision 30 June 2013; initially published on the internet 1 July 2013) Corresponding author C. A. Lindgren: Grinnell College, Division of Biology, 1116 8th Ave., Grinnell College, Grinnell, IA 50112, USA. E mail: [email protected] Abbreviations ACh, acetylcholine; 2-AG, 2-arachidonylglycerol; -BTX, -bungarotoxin; CB1 , cannabinoid form 1; COX, cyclooxygenase; DIC, differential interference contrast; DTC, D-tubocurarine chloride; eCB, endocannabinoid; EPP, end-plate possible; GCP, glutamate carboxypeptidase; L-NAME, N G -nitro-L-arginine methyl ester; MEPP, miniature end-plate potential; mAChR, muscarinic acetylcholine receptor; NAAG, N -acetylaspartylglutamate; nAChR, nicotinic acetylcholine receptor; NMDA, N -methyl-D-aspartate; NMJ, neuromuscular junction; NO, nitric oxide; NOS, nitric oxide synthase; PSC, perisynaptic Schwann cell; PGD2 -G, prostaglandin D2 glycerol ester; PGE2 -G, prostaglandin E2 glycerol ester.[Ir(Cp-)Cl2]2 manufacturer Introduction Since the discovery of endocannabinoids (eCBs) considerably study has focused on the function of membrane-derived lipids in synaptic plasticity.PMID:33397164 At most synapses, eCBs are released from the postsynaptic cell in response to depolarization (Ohno-Shosaku et al. 2001; Wilson Nicoll, 2001) and/or the activation of metabotropic receptors, for instance muscarinic acetylcholine (ACh) receptors (Kim et al. 2002; Fukudome et al. 2004). Once released, eCBs bind for the cannabinoid kind 1 (CB1 ) receptor on the presynaptic terminal and inhibit neurotransmitter release (Maejima et al. 2001). Though eCBs were initial shown to modulate synapses within the CNS, they have also been implica.