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Yuji Yoshikawa

Publications and source records attributed to Yuji Yoshikawa.

5 recordsLinked to original sources
PubMed2006

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.

Journal Article↗
PubMed2005

Involvement of P2X receptor subtypes in ATP-induced enhancement of the cough reflex sensitivity.

We examined the effect of inhaled ATP on the chemical irritant-induced coughs to clarify the roles of ionotropic purinergic receptors in these modulations. Although inhalation of 0.1 M citric acid by itself produced only a few coughs in guinea pigs, exposure to ATP, at concentrations of 3-10 microM, for 2 min concentration-dependently increased the number of 0.1 M citric acid-induced coughs. ATP-induced enhancement of the number of citric acid-induced coughs was abolished when animals were pretreated with 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5-triphosphate (TNP-ATP), an antagonist of P2X receptor subtypes P2X1-4, at a concentration of 50 microM, for 2 min. However, exposure to pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), an antagonist of P2X receptor subtypes P2X1,2,3,5,7, but not of P2X4 receptors, at a concentration of 50 microM, for 2 min, had no effect on the ATP-induced enhancement of the number of citric acid-induced coughs. Furthermore, exposure to reactive blue 2 (RB2, 30 microM, 2 min), an antagonist of P2Y receptors, had no effect on the ATP-induced enhancement of the number of citric acid-induced coughs. Exposure to ATP, at a concentration of 10 microM, for 2 min significantly increased the number of citric acid-induced coughs in capsaicin-pretreated guinea pigs. Furthermore, ATP had no effect on the number of capsaicin-induced coughs in naive animals. These results suggest that although ATP, by itself, does not elicit spontaneous coughs, it likely enhances the cough reflex sensitivity. Furthermore, stimulation of P2X receptors, especially P2X4 receptors, on rapidly adapting receptors may be required for the ATP-induced enhancement of the cough reflex sensitivity.

Adenosine Triphosphate↗
PubMed2005

Role of delta-opioid receptor subtypes in anxiety-related behaviors in the elevated plus-maze in rats.

RATIONALE: Recent studies have shown that endogenous opioid systems are associated with the regulation of emotional responses. In particular, it has been reported that delta-opioid receptors act naturally to inhibit stress and anxiety. OBJECTIVE: The present study was designed to examine the possible involvement of opioid delta-receptor subtypes in the anxiety-related behavior in the elevated-plus-maze test. METHODS: Six-week-old male Lewis rats were used. The total numbers of visits to the closed and open arms and the cumulative time spent and visits in the open arms were determined. Plasma corticosterone levels were measured by enzyme immunoassay. RESULTS: Naltrindole (NTI), a delta-opioid receptor antagonist (3 mg/kg s.c.), induced a significant decrease in the percentages of time spent and visits in the open arms. Naltriben (NTB), a delta2-opioid receptor antagonist (3 mg/kg s.c.), but not 7-benzylidenenaltrexone, a delta1-opioid receptor antagonist, produced similar anxiety-related behaviors in the elevated plus-maze. These effects of NTI and NTB were antagonized by pretreatment with (+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80), a delta-opioid receptor agonist. Furthermore, after exposure to the elevated plus-maze, the maximal increase in the plasma corticosterone level in NTI-treated rats was clearly higher than that in vehicle-treated rats. However, when NTI and SNC80 were coadministered, higher levels of plasma corticosterone were not seen after exposure to the elevated plus-maze. CONCLUSION: These results suggest that endogenous delta2-opioid-receptor-mediated systems are involved in the regulation of anxiety-related behaviors and might play a physiologically important role in the regulation of adrenocortical activity.

Animals↗
PubMed2005

Effect of cigarette smoke exposure in vivo on bronchial smooth muscle contractility in vitro in rats.

Cigarette smoking is a risk factor for the development of airway hyperresponsiveness and chronic obstructive pulmonary disease. Little is known concerning the effect of cigarette smoking on the contractility of airway smooth muscle. The current study was performed to determine the responsiveness of bronchial smooth muscles isolated from rats that were subacutely exposed to mainstream cigarette smoke in vivo. Male Wistar rats were exposed to diluted mainstream cigarette smoke for 2 h/d every day for 2 wk. Twenty-four hours after the last cigarette smoke exposure, a marked airway inflammation (i.e., increases in numbers of neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid and peribronchial tissues) was observed. In these subacutely cigarette smoke-exposed animals, the responsiveness of isolated intact (nonpermeabilized) bronchial smooth muscle to acetylcholine, but not to high K+ -depolarization, was significantly augmented when compared with the air-exposed control group. In alpha-toxin-permeabilized bronchial smooth muscle strips, the acetylcholine-induced Ca2+ sensitization of contraction was significantly augmented in rats exposed to cigarette smoke, although the contraction induced by Ca2+ was control level. Immunoblot analyses revealed an increased expression of RhoA protein in the bronchial smooth muscle of rats that were exposed to cigarette smoke. Taken together, these findings suggest that the augmented agonist-induced, RhoA-mediated Ca2+ sensitization may be responsible for the enhanced bronchial smooth muscle contraction induced by cigarette smoking, which has relevance to airway hyperresponsiveness in patients with chronic obstructive pulmonary disease.

Acetylcholine↗