Tetsuro Yamaguchi

Effect of Cigarette Smoking on Prevalence of Summer-type Hypersensitivity Pneumonitis Caused by Trichosporon Cutaneum

We investigated the effect of cigarette smoking on the prevalence of summer-type hypersensitivity pneumonitis (SHP) caused by Trichosporon cutaneum. In the adult family members of SHP patients, we found that 27 of 41 (65.9%) nonsmokers were SHP patients, compared with 3 of 11 (27.3%) smokers (p less than .05). Also, the prevalence of anti-T. cutaneum antibody was significantly lower in the smokers (p less than .05). A questionnaire provided to 209 SHP patients revealed that the smoking rates of male and female SHP patients were significantly lower (p less than .01) than rates in the normal Japanese population. However, no difference was found in serum anti-T. cutaneum antibody activities or the bronchoalveolar lavage lymphocyte phenotypes for smoking and nonsmoking SHP patients. It was concluded that cigarette smoking had a suppressive effect on the outbreak of SHP, but smoking caused no further suppression after the disease was established.

Tachykinin antagonist FK224 inhibits neurokinin A‐, substance P‐ and capsaicin‐induced human bronchial contraction

Summary— To determine the roles of endogenously released tachykinins (substance P [SP] and neurokinin A [NKA]) in the human bronchial tissues, we studied the effects of tachykinin antagonist FK224 on bronchial smooth muscle contraction induced by SP, NKA and capsaicin in an organ bath. FK224 (10−6 M and 10−5 M, respectivly) significantly inhibited NKA‐induced contraction and 10−5 M FK224 shifted the dose‐response curve to more than one log unit higher concentration. Because SP‐ and capsaicin‐induced contractions were small, we pretreated the tissues with the neutral endopeptidase inhibitor phosphoramidon (10−5 M), which inhibits degradation of exogenous tachykinins in order to potentiate the contractions. FK224 (10−5 M) significantly inhibited SP‐induced contraction and it shifted the dose‐response curves to about one log unit higher concentration. FK224 (10−5 M) also significantly inhibited capsaicin‐induced contraction and it shifted the dose‐response curves to more than one log unit higher concentration. In contrast, FK224 (10−5 M) did not affect on acetylcholine‐, histamine‐, and leukotriene D4‐induced contraction. These results suggest that FK224 is a tachykinin receptor antagonist in the human bronchial smooth muscle, and that capsaicin‐induced contraction is due to endogenously released tachykinin‐like substances in the human bronchus.

Evidence that allergen-induced contraction of guinea pig bronchi is mediated in part by the release of tachykinins

To study the role of tachykinins in allergic responses in the airways of guinea pigs sensitized to ovalbumin (OVA), we examined the bronchial contractile response to allergen in the presence or absence of the tachykinin antagonist FK224 in vitro. Because neutral endopeptidase (NEP) effectively cleaves tachykinins, we incubated bronchial tissues with the NEP inhibitor phosphoramidon (10(-5) M) to maintain the activity of endogenously released tachykinins. Then we added 10(-5)% (10 microns/ml) OVA in the presence or absence of FK224 (10(-5) M). FK224 significantly inhibited OVA-induced contraction plateaued and began to relax, we added 10(-5) M phosphoramidon. In the tissue without FK224, phosphoramidon blocked the relaxation and enhanced the contraction. In contrast, in the tissues treated with FK224, phosphoramidon did not enhance the OVA-induced contraction. The enhancement of the contraction induced by phosphoramidon was not inhibited by the sodium channel blocker tetrodotoxin. These results suggest that (1) allergic response causes release of tachykinin-like substances to induce bronchial contraction in part, (2) these responses are blocked by tachykinin antagonist FK224 and (3) nerve conduction is not necessary for the release of tachykinin-like substances induced by allergic response in the guinea pig bronchus.