| Project/Area Number |
13670833
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Dokkyo University School of Medicine |
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Principal Investigator |
YOSHIHARA Shigemi Dokkyo University School of Medicine, Medicine, Assistant Professor, 医学部, 講師 (80220713)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Yumi Dokkyo University School of Medicine, Medicine, Instructor, 医学部, 助手 (00306200)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Asthma / Bronchodilator / β2-adrenoceptor agonist / Salbutamol / PACAP 1-27 / PACAP 1-27 analogue / Airway smooth muscle / Human bronchi / β_2刺激薬 |
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| Research Abstract |
We compared the relaxant effect of pituitary adenylate cyclase activating peptide (PACAP) 1-27 with that of a newly developed PACAP 1-27 analogue, [Arg_<152021>Leu_<17>]-PACAP-Gly-Lys-Arg-NH_2, in human bronchi in vitro. In human bronchi precontracted by carbachol concentration (0.1μM), cumulative administration of PACAP 1-27 and salbutamoi caused concentration-dependent smooth muscle relaxation with similar potencies and maximum relaxant effects. Non-cumulative administration of the PACAP 1-27 analogue and the original PACAP 1-27 caused concentration-dependent relaxation with a similar maximum relaxant effect and potency as well. However, the onset and offset of action was markedly slower for the PACAP 1-27 analogue than for the original PACAP 1-27 (>90% versus <10% of peak relaxation remaining 5h after administration). Peptidase inhibition by captopril (10μM) and phosphoramidon (1μM) significantly increased the maximum relaxant effect and duration of action of PACAP 1-27 but not of the PACAP 1-27 analogue, during the 3h of observation in the human bronchi. We conclude that [Arg_<152021>Leu_<17>]-PACAP-Gly-Lys-Arg-NH_2 produce significant, concentration-dependent and sustained airway smooth muscle relaxation in vitro. The sustained relaxant effect is due, at least in part, to the PACAP 1-27 analogue being less susceptible to cleavage by peptidases than the original peptide PACAP 1-27.
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