Adrenocorticotropic hormone-releasing activity of urotensin I and its fragments in vitro.

Adrenocorticotropic hormone (ACTH)-releasing activity of synthetic carp Urotensin I (UI) and its ten synthetic fragments were examined using cultured rat pituitary cells. Both UI(1-41) and rat CRF (rCRF) increased ACTH release in a similar fashion at a concentration range from 10 pM to 100 nM. The potency of UI(1-41) was about one seventh that of rCRF on a molar basis. Four of ten UI fragments, UI(1-36), UI(4-36), UI(6-36) and UI(1-19) showed relatively strong ACTH-releasing activity, whereas both UI(9-36) and UI(17-36) showed extremely weak ACTH-releasing activity. However, all these fragments showed the activity in a dose-dependent manner parallel with that of UI(1-41). The activity of UI(1-36) was weaker than UI(1-41), suggesting that the C-terminal 37-41 sequence is required to express the full ACTH-release activity, although each of four C-terminal fragments, UI(24-36), UI(24-41), UI(29-36) and UI(29-41), exhibited no activity. In summary, the 4-19 amino acid sequence of UI( is important to exhibit ACTH-releasing activity and the C-terminal 37-41 sequence will be necessary to express the full activity. (C) Munksgaard 1997.