PACAP and gastrin regulate the histidine decarboxylase promoter via distinct mechanisms.

Autor: McLaughlin, John T., Wandong Ai, Sinclair, Natalie F., Colucci, Rocchina, Raychowdhury, Raktima, Koh, Theodore J., Wang, Timothy C.
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Zdroj: American Journal of Physiology: Gastrointestinal & Liver Physiology; Jan2004, Vol. 286, pG51-G59, 9p, 2 Black and White Photographs, 18 Graphs
Abstrakt: The enterochromaffin-like (ECL) cell controls gastric acid secretion via histamine, generated by L-histidine decarboxylase (HDC). HDC expression is regulated by gastrin. However, gastrin is not alone in controlling ECL cell function. For example, the neural peptide pituitary adenylate cyclase-activating polypeptide (PACAP) also increases ECL cell proliferation. To investigate a potential role of PACAP in regulating HDC expression, we generated a series of HDC promoter-luciferase reporter constructs and transiently transfected them into PC12 cells (stably expressing the gastrin-CCK-2 receptor). We found that PACAP regulates HDC promoter activity. This is temporally biphasic, involving both adenyl cyclase and phospholipase C-dependent pathways. Deletional analysis, block mutation, and EMSA demonstrated a PACAP-response element at -177 to -170, wholly necessary for the effects of PACAP and discrete from known gastrin-responsive elements. Discrete neural and endocrine pathways regulate ECL cells through different patterns of postreceptor signaling and promoter activation, which may be appropriate to their functions in vivo. histamine [ABSTRACT FROM AUTHOR]
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