Participation of thromboxane A(2) in the cough response in guinea-pigs: antitussive effect of ozagrel.

1. The purpose of this study was to investigate the involvement of thromboxane A(2) (TXA(2)) in the cough response in a guinea-pig cough model. Here, we describe results obtained using a selective TXA(2) synthetase inhibitor, ozagrel, and a selective TXA(2) agonist, U-46619. 2. Guinea-pigs were anaesthetized and exposed to an aerosol of capsaicin (100 microM) to elicit coughing. The number of coughs was 20.0+/-5.8 during capsaicin provocation (5 min), but only 2. 8+/-0.4 during a 5-min inhalation of phosphate-buffered saline (PBS) (P:<0.05). 3. TXB(2) levels in BAL were 101.4+/-8.0 and 58.4+/-8.7 pg ml(-1) following capsaicin and PBS inhalation, respectively (P:<0. 01), but there was no intergroup difference in the cell populations in BAL. 4. Inhalation of U-46619 did not induce a cough response by itself at concentrations of 100 ng ml(-1) to 10 microg ml(-1). However, it caused a 2 fold increase in the number of capsaicin-induced coughs. 5. To explore the source of the TXA(2), BAL cells were stimulated with capsaicin and the supernatants collected for analysis. The TXB(2) concentration in BAL was increased dose-dependently, indicating that TXA(2) is released from BAL cells in response to capsaicin. 6. Ozagrel was administered orally 1 h before a 5 min capsaicin provocation and the number of coughs was counted during the capsaicin inhalation. Ozagrel decreased the number of coughs dose-dependently (ED(50) value, 26.3 mg kg(-1)). 7. These results show that TXA(2) modulates the capsaicin-induced cough response by increasing capsaicin-sensitivity.

Inhibition of interleukin 5 production with no influence on interleukin 4 production by an anti-allergic drug, tranilast, in Toxocara canis-infected mice.

Tranilast is well-known as a useful drug for allergic diseases. This drug is believed to exhibit its therapeutic effects by inhibiting the release of chemical mediators from mast cells and basophils. Effects of tranilast on T helper type 2 (Th2) cytokine production were investigated in mice infected with Toxocara canis (Tc). Tranilast reduced interleukin (IL)-5 production in a dose-dependent manner but not IL-4 production at all in lung and spleen cells from Tc-infected mice cultured under stimulation with excretory-secretory antigen. Obvious IL-5 mRNA expression was observed at week 1 in the lung alone, and IL-4 mRNA expression was detected at similar levels at weeks 1-6 of infection in both lung and spleen. IL-5 but not IL-4 mRNA expression in the lung was significantly inhibited by daily administration of 100 mg/kg of tranilast for 1 week. This treatment also reduced the serum IL-5 level. Thus, tranilast inhibited IL-5 but not IL-4 production either in vitro or in vivo. The results imply that IL-5 and IL-4 production by Th2 cells may be controlled through different mechanisms.

Morphogenic activity of fibroblast growth factor-2 on primary neural precursor cells in three-dimensional culture.

Mouse neural precursor cells (NPC) were dissociated from fetal heads at the 10th day of gestation. When clumps of NPC were cultured in collagen gel, they grew and reorganized neural tube-like structures in medium containing fetal calf serum at 10% and supplemented with insulin, transferrin, cholera toxin and selenite. However, dissociated NPC died when they were cultured in collagen gel at low density in the same medium. Addition of fibroblast growth factor-2 (FGF-2) to this culture stimulated growth of NPC and formation of neural tube-like structures. The requirement for FGF-2 disappeared in high seeding density culture: they grew and formed neural tube-like structures without FGF-2. The structures formed in collagen gel were immunohistochemically positive against anti-FGF-2 antibody. The results show that the three-dimensional culture system provides a useful tool to study the roles of FGF-2 in morphogenesis of the central nervous system.