Kitabgi P, Dubuc I, Nouel D, Costentin J, Cuber J C, Fulcrand H, Doulut S, Rodriguez M, Martinez J
Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, Sophia Antipolis, Valbonne, France.
Neurosci Lett. 1992 Aug 17;142(2):200-4. doi: 10.1016/0304-3940(92)90373-f.
The effects of the endopeptidase 24.11 ('enkephalinase') inhibitor thiorphan, the aminopeptidase inhibitor bestatin and a novel metallopeptidase inhibitor JMV 390-1 on the K(+)-evoked release of immunoreactive neurotensin and neuromedin N (iNT and iNN) from mouse hypothalamic slices were examined. (JMV 390-1 inhibits several metallopeptidases including endopeptidases 24.11, 24.15 and 24.16, and aminopeptidase N equipotently with Ki values around 50 nM.) Thiorphan increased the recovery of released iNT nearly 2-fold and had no effect on iNN. Bestatin produced a 4-fold increase in iNN recovery and was inactive on iNT. Finally, iNT and iNN recoveries were increased up to 4- and 5-fold, respectively, by JMV 390-1. These results show that in the mouse hypothalamus endopeptidase 24.11 participates with other metalloendopeptidases to the degradation of endogenously released NT while endogenously released NN is principally degraded by aminopeptidase(s).
研究了内肽酶24.11（“脑啡肽酶”）抑制剂硫喷妥、氨肽酶抑制剂贝司他汀和新型金属肽酶抑制剂JMV 390-1对钾离子诱发的小鼠下丘脑切片中免疫反应性神经降压素和神经介素N（iNT和iNN）释放的影响。（JMV 390-1能同等程度地抑制多种金属肽酶，包括内肽酶24.11、24.15和24.16，以及氨肽酶N，其Ki值约为50 nM。）硫喷妥使释放的iNT回收率提高了近2倍，对iNN没有影响。贝司他汀使iNN回收率提高了4倍，对iNT没有作用。最后，JMV 390-1使iNT和iNN回收率分别提高了4倍和5倍。这些结果表明，在小鼠下丘脑中，内肽酶24.11与其他金属内肽酶共同参与内源性释放的NT的降解，而内源性释放的NN主要由氨肽酶降解。
