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Histidyl-proline diketopiperazine. Novel formation that does not originate from thyrotropin-releasing hormone.

1993; Elsevier BV; Volume: 268; Issue: 28 Linguagem: Inglês

10.1016/s0021-9258(19)36865-6

1083-351X

Kazuya Miyashita, Masami Murakami, Masanobu Yamada, T. Iriuchijima, Masataka Mori,

Neuropeptides and Animal Physiology

We asked whether cyclo(His-Pro) may arise from a substance other than the initially found progenitor thyrotropin-releasing hormone (TRH). Incubation of TRH-Gly (pGlu-His-Pro-Gly), a TRH precursor, with brain hypothalamic cytosols caused significant formation of His-Pro-Gly followed by the generation of histidyl-proline diketopiperazine (cyclo(His-Pro)), whereas TRH was not formed. The addition of purified pyroglutamyl aminopeptidase resulted in the transformation of TRH-Gly to His-Pro-Gly and cyclo (His-Pro) but not to TRH. Neither TRH nor cyclo(His-Pro) was produced from TRH-Gly in the presence of alpha-amidating enzyme under the present conditions. Nonenzymatic conversion of His-Pro-Gly to cyclo(His-Pro) occurred. The present results provide evidence that cyclo(His-Pro) can emanate from a direct predecessor form of TRH by pyroglutamyl aminopeptidase action, not through TRH formation.