Shore S A, Sharpless C, Drazen J M
Respiratory Biology Program, Harvard School of Public Health, Boston, Massachusetts 02115.
Pulm Pharmacol. 1993 Jun;6(2):143-7. doi: 10.1006/pulp.1993.1018.
The effects of rapid intravenous infusions of gamma-preprotachykinin-(72-92)-peptide amide (neuropeptide gamma) or beta-preprotachykinin-(72-107)-peptide amide (neuropeptide K), two N-terminally extended forms of neurokinin A (NKA), on pulmonary mechanics were examined in anaesthetized mechanically ventilated guinea-pigs. Neuropeptide gamma (NP gamma) and neuropeptide K (NPK) each caused dose-related decreases in pulmonary conductance (GL). The rank order of potency as bronchoconstrictors for the three peptides was NPK > NP gamma > NKA. Pretreatment of guinea-pigs with the neutral endopeptidase (NEP) inhibitor SCH32615 (1 mg/kg iv) decreased the doses of NP gamma and NKA required to cause a 50% decrease in GL by 3.8- and 4.9-fold respectively, but did not significantly alter NPK-induced bronchoconstriction. In animals without SCH32615, the time course of bronchoconstriction was similar for NKA and NP gamma, but NPK caused significantly more prolonged changes in GL. SCH32615 did not alter the time course of bronchoconstriction induced by NKA or NPK, but prolonged the changes in GL induced by NP gamma. The results indicate that post-translational processing of gamma- and beta-preprotachykinin mRNAs to yield NP gamma and NPK instead of NKA results in an enhanced duration of effect and an increase in bronchoconstrictor potency.
在麻醉状态下进行机械通气的豚鼠中，研究了快速静脉输注γ-前速激肽原-（72-92）-肽酰胺（神经肽γ）或β-前速激肽原-（72-107）-肽酰胺（神经肽K）这两种神经激肽A（NKA）的N端延伸形式对肺力学的影响。神经肽γ（NPγ）和神经肽K（NPK）均引起肺传导率（GL）呈剂量相关的降低。三种肽作为支气管收缩剂的效力排序为：NPK＞NPγ＞NKA。用中性内肽酶（NEP）抑制剂SCH32615（1mg/kg静脉注射）预处理豚鼠，可使引起GL降低50%所需的NPγ和NKA剂量分别减少3.8倍和4.9倍，但未显著改变NPK诱导的支气管收缩。在未使用SCH32615的动物中，NKA和NPγ引起支气管收缩的时间进程相似，但NPK引起的GL变化持续时间明显更长。SCH32615未改变NKA或NPK诱导的支气管收缩时间进程，但延长了NPγ诱导的GL变化持续时间。结果表明，γ-和β-前速激肽原mRNA经翻译后加工产生NPγ和NPK而非NKA，导致作用持续时间延长和支气管收缩效力增加。
