Effect of N-arachidonoyl-(2-methyl-4-hydroxyphenyl) amine (VDM11), an anandamide transporter inhibitor, on capsaicin-induced cough in mice

BACKGROUND: Several observations have suggested that anandamide, an endogenous cannabinoid ligand, plays an important role in the modulation of cough sensitivity. However, it is unknown whether the anandamide membrane transporter plays a role in this modulation. To test this hypothesis, we investigated the effects of VDM11, an anandamide membrane transporter inhibitor, on capsaicin- and anandamide-induced cough. METHODS: The effect of VDM11, an anandamide membrane transporter inhibitor, on capsaicin- and anandamide-induced cough in mice was examined. RESULTS: VDM11, at doses of 3–10 mg/kg subcutaneously, produced a dose-dependent antitussive effect. This antitussive effect was antagonized by pretreatment with either intraperitoneal administration (3 mg/kg) or inhalation (1 mg/ml) of SR141716A, a cannabinoid receptor (CB1) antagonist. However, intracerebroventricular injection of SR141716A (0.03 mg/mouse) did not alter the effect of VDM11. Exposure of mice to a nebulized solution of 10% DMSO, a vehicle of anandamide, induced a cough response (7.7 ± 0.6 coughs/3 min; n = 10). Exposure of mice to a nebulized solution of anandamide, at concentrations of 0.03, 0.3 and 3 mg/ml, also produced a cough response in a concentration-dependent manner. The number of coughs induced by low dose (0.03 mg/ml) anandamide was significantly less than that of 10% DMSO. On the other hand, the number of coughs induced by high dose (3 mg/ml) anandamide was significantly greater than that of 10% DMSO. When AM251 (1.8 mM), a selective CB1 receptor antagonist, was given by aerosol for 4 min before inhalation of 0.03 mg/ml of anandamide, the number of coughs was significantly increased to the level observed with 10% DMSO alone. When capsazepine (0.3 mM), a selective TRPV1 receptor antagonist, was given via aerosol for 4 min before inhalation of 3 mg/ml of anandamide, the number of coughs was significantly decreased to the levels observed with 10% DMSO alone. The number of coughs induced by high dose (3 mg/ml) anandamide was significantly and dose-dependently reduced by the pretreatment with VDM11. CONCLUSION: These results suggest that anandamide, an endogenous cannabinoid ligand, may modulate cough sensitivity and that anandamide transporters play an important role in this modulation. Furthermore, these findings indicate that inhibition of the uptake of anandamide produced a potent antitussive effect and suggests that the anandamide transporter may be a potential target for peripherally acting antitussive drugs

Effects of Rising Temperature on Grain Quality, Palatability and Physicochemical Properties of Rice

The effect of high temperatures on grain quality, palatability of cooked rice and physicochemical characteristics of rice was examined in a temperature gradient chamber (TGC). Experimental plots going from TG1 (near the air intake side) and TG4 (near the air exhaust side) along the temperature gradient in TGC, corresponding to low and high temperature, and an open field plot (outside of TGC) were arranged. The mean and maximum air-temperatures in TG4 were 2.8 °C and 5.9 °C higher, respectively, than those in TG1. Brown rice yield per m2 in outside (572 g) was the highest, and those in TG1 (503 g) and TG4 (180 g) were 12.1 and 68.6ｵ lower than outside, respectively. This yield decline was due to the decrease in the number of panicles and percentage of ripened grains, and an increase in the percentage of sterile spikelets. Most of the immature grain was milky white grains (10.8ﾝ14.6ｵ) and white berry grains (10.7ﾝ43.4ｵ), and other white immature grain accounted for only 0ﾝ2.6ｵ. The grains from the outside plot were separated into perfect grain and milky white grain. The overall eating quality (＋3 to －3) was in the order of perfect grains (0.31) ＞ outside (0.00) ＞ milky white grains (－0.56) ＞ TG1 (－1.0) ＞ TG4 (－1.44). This indicates that the palatability of perfect and milky white grains was superior to and inferior to that of normal grain, and high temperatures deteriorate the eating quality of cooked rice. In the physicochemical characteristics of rice, the protein content showed a small variation (8.6ﾝ8.9ｵ) between normal, perfect and milky white grains, but that in TG1 (9.9ｵ) and TG4 (9.8ｵ) were higher than that in the outside. Amylose content of each plot was in the same order as the overall eating quality. This showed that amylose content did not affect the palatability because amylose content is normally negatively correlated with overall eating quality. H/-H ratio, a texture characteristic, was smaller in perfect grains than in normal grains, and that in milky white grains was larger than normal grains. This shows that the higher the share of milky white grains, the higher the H/-H ratio. Despite the superior eating quality, H/-H in TG1 was larger than that in TG4. Thus, the effect of H/-H ratio on the palatability of cooked rice grown in TGC was not clear