Charli J L, Mendez M, Joseph-Bravo P, Wilk S
Neuropeptides. 1987 May-Jun;9(4):373-8. doi: 10.1016/0143-4179(87)90010-2.
Pyroglutamyl diazomethyl ketone and N-benzyloxycarbonyl prolyl prolinal, specific inhibitors of pyroglutamyl peptidase I and prolyl endopeptidase respectively, were used to study the possible role of these enzymes in the regulation of thyrotropin releasing hormone turnover. In vitro thyrotropin releasing hormone release by male rat hypothalamic slices was studied. Combined in vitro treatment with 10(-5)M of both inhibitors totally inhibited both enzymatic activities. The treatment did not affect basal or 56 mM K+ induced thyrotropin releasing hormone release or thyrotropin releasing hormone levels in slices. Repeated combined intraperitoneal injections of the two inhibitors for up to 12 hours produced a 70%-95% reduction in mouse brain pyroglutamyl peptidase I specific activity and a 65%-85% reduction in prolyl endopeptidase specific activity. Thyrotropin releasing hormone levels were unaffected by this treatment in all regions tested. The data suggest that these two enzymes are not involved in the intra- or extracellular control of thyrotropin releasing hormone levels in brain or hypophysis.
焦谷氨酰重氮甲基酮和N-苄氧羰基脯氨酰脯氨醛分别是焦谷氨酰肽酶I和脯氨酰内肽酶的特异性抑制剂，被用于研究这些酶在促甲状腺激素释放激素代谢调节中的可能作用。对雄性大鼠下丘脑切片的体外促甲状腺激素释放激素释放情况进行了研究。用10⁻⁵M的两种抑制剂进行联合体外处理完全抑制了两种酶的活性。该处理不影响基础状态下或56 mM K⁺诱导的促甲状腺激素释放激素释放，也不影响切片中促甲状腺激素释放激素的水平。对两种抑制剂进行长达12小时的反复联合腹腔注射，使小鼠脑焦谷氨酰肽酶I的比活性降低了70% - 95%，脯氨酰内肽酶的比活性降低了65% - 85%。在所测试的所有区域中，促甲状腺激素释放激素水平不受该处理的影响。数据表明，这两种酶不参与脑或垂体中促甲状腺激素释放激素水平的细胞内或细胞外调控。
