Abstract：
BACKGROUND AND PURPOSE:GPR18 is a recently deorphaned lipid receptor that is activated by the endogenous lipid N-arachidonoyl glycine (NAGly) as well the behaviourally inactive atypical cannabinoid, abnormal cannabidiol (Abn-CBD). The presence and/or function of any GPR18-based ocular signalling system remain essentially unstudied. The objectives of this research are: (i) to determine the disposition of GPR18 receptors and ligands in anterior murine eye, (ii) examine the effect of GPR18 activation on intraocular pressure (IOP) in a murine model, including knockout mice for CB₁, CB₂ and GPR55. EXPERIMENTAL APPROACH:IOP was measured in mice following topical application of Abn-CBD, NAGly or the GPR55/GPR18 agonist O-1602, alone or with injection of the GPR18 antagonist, O-1918. GPR18 protein localization was assessed with immunohistochemistry. Endocannabinoids were measured using LC/MS-MS. KEY RESULTS:GPR18 protein was expressed most prominently in the ciliary epithelium and the corneal epithelium and, interestingly, in the trabecular meshwork. The GPR18 ligand, NAGly, was also detected in mouse eye at a level comparable to that seen in the brain. Abn-CBD and NAGly, but not O-1602, significantly reduced IOP in all mice tested. The antagonist, O-1918, blocked the effects of Abn-CBD and NAGly. CONCLUSIONS AND IMPLICATIONS:We present evidence for a functional GPR18-based signalling system in the murine anterior eye, including receptors and ligands. GPR18 agonists, Abn-CBD and NAGly, reduce IOP independently of CB₁, CB₂ or GPR55. These findings suggest that GPR18 may serve as a desirable target for the development of novel ocular hypotensive medications.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Caldwell MD,Hu SS,Viswanathan S,Bradshaw H,Kelly ME,Straiker Adoi
10.1111/bph.12136subject
Has Abstractpub_date
2013-06-01 00:00:00pages
834-43issue
4eissn
0007-1188issn
1476-5381journal_volume
169pub_type
杂志文章abstract：BACKGROUND AND PURPOSE:The bladder urothelium is now known to have active properties. Our aim was to investigate the contractile properties of the urinary mucosa in response to the tachykinin neurokinin A (NKA) and carbachol. EXPERIMENTAL APPROACH:Discrete concentration-response curves for carbachol and NKA were obtai...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.29
更新日期：2008-04-01 00:00:00
abstract：:Obesity has reached epidemic proportions in the Western society and is increasing in the developing world. It is considered as one of the major contributors to the global burden of disability and chronic diseases, including autoimmune, inflammatory and degenerative diseases. Research conducted on obesity and its compl...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14181
更新日期：2018-05-01 00:00:00
abstract：:1. The effects of 2-amino-5-phosphonovalerate and kynurenate, either alone or in combination, were tested on responses evoked by the excitatory amino acid agonists quinolinate, ibotenate, N-methyl-D-aspartate and N-methyl-DL-aspartate by use of an in vitro preparation of mouse neocortex and artificial cerebrospinal fl...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb10328.x
更新日期：1988-03-01 00:00:00
abstract：:Two-state and operational models of both agonism and allosterism are compared to identify and characterize common pharmacological parameters. To account for the receptor-dependent basal response, constitutive receptor activity is considered in the operational models. By arranging two-state models as the fraction of ac...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.12231
更新日期：2013-07-01 00:00:00
abstract：:The binding of [3H]-iloprost (ZK36374) to NCB-20 membranes revealed a single population of high affinity receptors (KD = 9.55 nM, Bmax = 431 fmol mg-1 protein) and a low affinity, non-saturable binding component. Desensitization of prostacyclin-responsiveness of NCB-20 cells is induced by culture in the presence of th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb08852.x
更新日期：1985-05-01 00:00:00
abstract：:1. The present work describes the effects of inhibitors (amiloride and ethylisopropylamiloride) and activators (quinoxaline and phenylephrine) of the Na(+)-H+ exchanger on the outflow of dopamine in rat kidney slices loaded with L-dihydroxyphenylalanine (L-DOPA). 2. Incubation of kidney slices loaded with 50 microM L-...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13608.x
更新日期：1993-06-01 00:00:00
abstract：:1. The polymorphonuclear neutrophils (PMN) activation and mobilization observed in acute cerebral infarction contribute to the brain tissue damage, but PMN could also be involved in postischemic functional injury of ischemied blood vessel. 2. This study was undertaken to investigate whether pharmacological neutropenia...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706124
更新日期：2005-04-01 00:00:00
abstract：:1. The effects of chlorobutanol, a widely used drug preservative, on exocrine response and intracellular Ca2+ dynamics were examined in isolated pancreatic acini of the rat. 2. Chlorobutanol (1 mg ml-1) markedly inhibited the secretory response to cholecystokinin octapeptide (CCK-8), carbamylcholine chloride (carbacho...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13628.x
更新日期：1993-07-01 00:00:00
abstract：:1 Pinacidil relaxes blood vessels through opening the K(ATP) channels with a resultant membrane hyperpolarization and inhibition of Ca(2+) influx. The aim of this study was to examine the mechanisms thereby pinacidil induces K(+) channel-independent relaxation in isolated endothelium-denuded rat mesenteric artery. 2 P...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705062
更新日期：2003-02-01 00:00:00
abstract：:1. In this study we examined the effects of cortistatin, a putative endogenous ligand for somatostatin (SRIF) receptors, on the membrane properties of rat locus coeruleus (LC) neurones in vitro, by use of intracellular and whole cell patch clamp recording. We have compared the actions of cortistatin with those of SRIF...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701541
更新日期：1997-12-01 00:00:00
abstract：:Asthma is an inflammatory disease of the lungs and the transcription factor NF-kappa B regulates the production of numerous inflammatory mediators that may have a role in the pathogenesis of asthma. Hence, the signalling pathways leading to NF-kappa B activation are considered prime targets for novel anti-inflammatory...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706170
更新日期：2005-05-01 00:00:00
abstract：:Substance P and substance K (neurokinin A) (dose range: 0.08-80 nmol kg-1) were tested for their effects on gastrointestinal propulsion in the rat. The peptides were given by intraperitoneal injection concurrently with the intragastric administration of a test meal containing charcoal and 51Cr. Examination 3 min after...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb09462.x
更新日期：1985-09-01 00:00:00
abstract：:The stoichiometric relationship between adrenoceptors and saturable binding sites for 1,4-dihydropyridines in calcium channels was investigated in human ventricular myocardium. Membrane particles were prepared from heart specimens of patients undergoing open heart surgery. The patients suffered from hypertrophic obstr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11194.x
更新日期：1987-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:N-type voltage-gated calcium (Cav 2.2) channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Although Cav 2.2 channel antagonists are recommended as first-line treatment for neuropathic pain, calcium-current blocking ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13737
更新日期：2018-06-01 00:00:00
abstract：:1. In rats under ether anaesthesia, the left coronary artery was ligated and reperfused after 10 min of ischaemia. Forty-eight hours later the myocardium was analyzed for creatine kinase (CK) activity. 2. Human superoxide dismutase (h-SOD) given 1 min after occlusion and again 6 h later significantly improved survival...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11699.x
更新日期：1988-11-01 00:00:00
abstract：:1. Two quinozalinediones, FG9041 and FG9065, which had previously been shown to displace binding to the quisqualate receptor, were tested on rat neocortex and frog spinal cord in vitro against depolarizations induced by quisqualate, kainate and N-methyl-D-aspartate (NMDA). In both preparations effects of quisqualate w...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11680.x
更新日期：1988-10-01 00:00:00
abstract：:1 The concept that nitric oxide (NO) release can be beneficial in inflammatory conditions has raised more attention in the recent years, particularly with the development of nitric oxide-releasing anti-inflammatory drugs. There is considerable evidence that NO is capable of enhancing the anti-inflammatory benefits of ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705854
更新日期：2004-11-01 00:00:00
abstract：:Antihistamine induced cognitive decline was evaluated using positron emission tomography (PET) measurement of histamine H1 receptor (H1R) occupancy and regional cerebral blood flow (rCBF). Cognitive performance in attention-demanding task deteriorated dose-dependently and the effects were statistically significant aft...
journal_title：British journal of pharmacology
pub_type： 临床试验,杂志文章
doi：10.1038/sj.bjp.0702994
更新日期：2000-01-01 00:00:00
abstract：:1. We have investigated the cellular target of K(+) channel blockers responsible for the inhibition of the EDHF-mediated relaxation in the rat mesenteric artery by studying their effects on tension, smooth muscle cell (SMC) membrane potential and endothelial cell Ca(2+) signal ([Ca(2+)](endo)). 2. In arteries contract...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704348
更新日期：2001-11-01 00:00:00
abstract：:1. Exposure of depilated skin of guinea-pig to ultraviolet (u.v.) light for 20 s produces a prolonged inflammatory response.2. The erythaema becomes evident within 15-30 min after the exposure and progressively increases in intensity reaching its maximum by 4-6 hours. The erythaema persists over 24 hours.3. Increase i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08321.x
更新日期：1973-02-01 00:00:00
abstract：:1. Desensitization of the myocardial beta-adrenergic signal transduction pathway is an important mechanism which is involved in the progression of hypertensive heart disease. The aim of the present study was to evaluate the differential effects of chronic pharmacotherapy with an angiotensin converting enzyme (ACE)-inh...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701615
更新日期：1998-02-01 00:00:00
abstract：:1. The effects of low oxygen tension on tone and on the responsiveness to contractile and relaxant agents were examined on circumflex coronary artery rings isolated from sheep. 2. When artery rings (2-2.5 mm o.d.) were set at their optimal resting tension, introduction of hypoxia (0% O2) caused a sustained contraction...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11894.x
更新日期：1989-04-01 00:00:00
abstract：BACKGROUND:5-HT(2B) receptors are localized within the myenteric nervous system, but their functions on motor/sensory neurons are unclear. To explore the role of these receptors, we further characterized the 5-HT(2B) receptor antagonist RS-127445 and studied its effects on peristalsis and defecation. EXPERIMENTAL APPR...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00155.x
更新日期：2009-09-01 00:00:00
abstract：:1 The responses of excitatory junctions on locust skeletal muscle fibres to iontophoretically applied L-glutamic acid and DL-ibotenic acid, a rigidly extended analogue of glutamate, were recorded by means of intracellular microelectrodes.2 Iontophoresis of L-glutamate to junctional sites produced transient depolarizat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb13675.x
更新日期：1979-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Lung cancer is one of the leading causes of cancer death worldwide. Despite advances in therapy, conventional therapy is still the main treatment and has a high risk of chemotherapy resistance. Caspase-8 is involved in cell death and is a recognized marker for poor patient prognosis. EXPERIMENTA...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13176
更新日期：2015-08-01 00:00:00
abstract：:1. I.C.I. 50172 had marked quinidine-like effects on intracellular cardiac action potentials at concentrations above 20 mg/l. (6.61 x 10(-5)M). The rate of rise and overshoot of the action potential, conduction velocity and contractions were decreased. (-)-Propranolol had similar effects at less than 1/30 this concent...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1969.tb10576.x
更新日期：1969-10-01 00:00:00
abstract：:1. Gastric acid secretory responses to pentagastrin were characterized in the rat isolated gastric mucosa. In particular, the mechanisms underlying fade, declining response upon continued stimulation, and tachyphylaxis, progressively reduced responses upon repeated stimulation, were investigated. 2. Pentagastrin, 10(-...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11738.x
更新日期：1988-12-01 00:00:00
abstract：:The vanilloid receptor (VR1) is a ligand-gated ion channel, which plays an important role in nociceptive processing. Therefore, a pharmacological characterization of the recently cloned rat VR1 (rVR1) was undertaken. HEK293 cells stable expressing rVR1 (rVR1-HEK293) were loaded with Fluo-3AM and then incubated at 25 d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703390
更新日期：2000-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:N-arachidonoyl-serotonin (AA-5-HT) is an inhibitor of fatty acid amide hydrolase (FAAH)-catalysed hydrolysis of the endocannabinoid/ endovanilloid compound, anandamide (AEA). We investigated if AA-5-HT antagonizes the transient receptor potential vanilloid-1 (TRPV1) channel and, as FAAH and TRPV1...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707145
更新日期：2007-03-01 00:00:00
abstract：:1. The central and peripheral effects of the omega (benzodiazepine) site ligands, clonazepam, alpidem, zolpidem, triazolam, flumazenil, ethyl beta carboline-3-carboxylate (beta-CCE) and N-methyl beta carboline-3-carboxylate (beta-CCM) on intestinal myoelectrical activity were evaluated in conscious rats, chronically f...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb16204.x
更新日期：1994-09-01 00:00:00
