ストレスと神経ペプチド(ストレスと免疫)
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概要
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Substance P (SP), a potent neuropeptide, which localezed to sensory nerves and released by many physiological stimuli included in stress, has been implicated in airway neurologenic inflammation. We have studied the effects of capsaicin (CAP)-induced tachykinin release and exogenously applied SP on eosinophil (EOS) recruitment into the airway in guinea pigs in vivo. We aerosolized several concentrations of CAP or SP and its C-terminal octapeptide SO_<4-11> and N-terminal fragment SP_<1-9> to male guinea pigs. Respiratory resistance (Rrs) of guinea pigs was measured by an oscillation technique and histological studies of the bronchi were also made. Inhaled exposure of CAP and SP resulted in both significant inceases in Rrs with PC_<2000> CAP and SP of 0.97±0.25(×10_<-6>M) and 0.95±0.11(×10_<-6>M)(n=5), respectively. Both stimulations also provoked striking eosinophilia in the bronchi in time- and dose-dependent manners. SP_<4-11> was found to be similar potent as in SP_<1-1>1-evoked EOS migration, while SP_<1-9> was inactive up to concentrations of 10_<-4>M, indicating that the C-terminal fragment appered to be essential. A neutral endopeptidase inhibitor, phosphoramidon potentiated both CAP- and SP-induced EOS infiltration. By contrast, pretreatment with [D-Pro^<2>, D-Trp^<7,9>]-SP, an analogue of SP and its receptor antagonist, diminished the response. We conclude that SP is capable of causing a striking eosinophilia in the lung in vivo, and may contribute to the airway inflammation in patients with asthma. This would provide further support for a link between SP and EOS in asthma.
- 1992-01-08
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