Pharmacological evidence for thromboxane receptor heterogeneity:implications for the eye

The pharmacological activity of two novel thromboxane A2 (TxA2)- mimetics, AGN191976 and AGN192093, was investigated in vitro, using standard organ bath assays and human platelets, to determine potency and selectivity at various prostanoid (PG-) receptors. The effects of these compounds on intraocular pressure in Beagle dogs were then compared with U-46619, a widely employed and structurally different TP-receptor agonist. AGN191976 and AGN192093 were highly potent TP-receptor agonists in the rat aorta (EC50 of 0.32 and 1.3 nM, respectively) and human myometrium. Both compounds were approximately 10 to 50 fold more potent than U-46619. These contractile responses could be blocked with a potent TP-receptor antagonist, SQ29548. In human platelets, AGN191976 (EC50=16.3 nM) and U-46619 (EC50=538.3 nM) potently stimulated aggregation (TP-receptor mediated effect), whereas AGN192093 was a much weaker agonist (EC50=37.9 μM). AGN192093 was not a partial agonist in platelets, since it did not antagonize aggregation induced by AGN191976, U-46619, arachidonic acid or ADP. These results provide evidence for a subdivision of TP-receptors, and AGN192093 appears to be able to distinguish between TP-receptors in smooth muscle and platelets. In the Beagle dog eye, both AGN191976 and AGN192093 were highly potent and efficacious ocular hypotensives. Single 2.5 μg doses of drug decreased lOP by 11.4 (AGN191976) and 7.7 mm Hg (AGN192093) relative to the contralateral control eye. In contrast, U-46619 did not lower IOP. AGN191976, but not U- 46619, increased outflow facility in these animals, which is consistent with their effects on IOP. Neither compound caused miosis which is FP-receptor mediated in the dog. These studies suggest the existence of heterogeneous populations of TP-receptors. AGN191976 and AGN192093, two novel TP-receptor agonists, appear to be useful tools for the pharmacological distinction of TP-receptor subtypes

Nifedipine Enhances the Relaxant Effects of Cyclo-Oxygenase Inhibitors on the Bovine Ciliary Muscle

Background/Aims: The inhibition of cyclo-oxygenase (COX) enzymes and the blockade of Ca2+ channels play an important role in the regulation of smooth muscle relaxation. This study was designed to investigate the relaxant effects of celecoxib, DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone), and indomethacin, cyclo-oxygenase (COX-1 and -2) inhibitors, in the absence or presence of a nifedipine, L-type Ca2+ channel blocker, on bovine ciliary muscle. Methods: Ciliary muscle strips (n = 12) were mounted in organ baths and tested for changes in isometric tension in response to celecoxib, DFU, and indomethacin. The relaxant effects of celecoxib, DFU, and indomethacin on carbachol-induced contractions in the presence or absence of nifedipine were investigated. Results: Celecoxib (10(-7)-10(-4) M), DFU (10(-7)-10(-4) M), indomethacin (10(-7)-10(-4) M), and nifedipine (10(-7)-10(-4) M) inhibited the carbachol-induced contractions in a concentration-dependent manner. The Em x value of indomethacin was significantly higher than the E-max values of celecoxib and DFU in ciliary muscle (P 0.05). The relaxation responses by celecoxib, DFU, and indomethacin were significantly increased in the presence of nifedipine (10(-6) M). There were no significant differences between pEC50 and values of celecoxib, DFU, and indomethacin in the absence of nifedipine (10-6 M) (P > 0.05), but E-max values were significantly increased (P < 0.05). Conclusions: These results suggest that the celecoxib, DFU, and indomethacin cause relaxation in ciliary muscle precontracted with carbachol. Blockade of calcium channels with nifedipine in ciliary muscle may increase the relaxant effect of celecoxib, DFU, and indomethacin. The topical or systemic use of celecoxib, DFU, and indomethacin with nifedipine can cause blurred near vision due to ciliary muscle relaxation, and in ocular pain conditions caused by ciliary spasm, the pain can be decreased more easily by combined use of these drugs

ECCE unpolarized TMD measurements

We performed feasibility studies for various measurements that are related to unpolarized TMD distribution and fragmentation functions. The processes studied include semi-inclusive Deep inelastic scattering (SIDIS) where single hadrons (pions and kaons) were detected in addition to the scattered DIS lepton. The single hadron cross sections and multiplicities were extracted as a function of the DIS variables $x$ and $Q^2$, as well as the semi-inclusive variables $z$, which corresponds to the momentum fraction the detected hadron carries relative to the struck parton and $P_T$, which corresponds to the transverse momentum of the detected hadron relative to the virtual photon. The expected statistical precision of such measurements is extrapolated to accumulated luminosities of 10 fb$^{-1}$ and potential systematic uncertainties are approximated given the deviations between true and reconstructed yields

Exclusive J/ψ detection and physics with ECCE

The EIC Comprehensive Chromodynamics Experiment (ECCE) detector has been recommended as a reference design for the proposed Electron-Ion Collider (EIC) program. This paper presents simulation studies of exclusive J/ detection and selected physics impact results in EIC using the projected ECCE detector concept. Exclusive quarkonium photoproduction is one of the most popular processes in EIC, which has a large cross section and a simple final state. Due to the gluonic nature of the exchange Pomeron, this process can be related to the gluon distributions in the nucleus. Preliminary results estimate the excellent statistics benefited from the large cross section of J/ photoproduction and superior performance of ECCE detector concept. The precise measurement of exclusive J/ photoproduction at EIC will help us to more deeply understand nuclear gluon distributions, near threshold production mechanism and nucleon mass structure

Open Heavy Flavor Studies for the ECCE Detector at the Electron Ion Collider

International audienceThe ECCE detector has been recommended as the selected reference detector for the future Electron-Ion Collider (EIC). A series of simulation studies have been carried out to validate the physics feasibility of the ECCE detector. In this paper, detailed studies of heavy flavor hadron and jet reconstruction and physics projections with the ECCE detector performance and different magnet options will be presented. The ECCE detector has enabled precise EIC heavy flavor hadron and jet measurements with a broad kinematic coverage. These proposed heavy flavor measurements will help systematically study the hadronization process in vacuum and nuclear medium especially in the underexplored kinematic region