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Vascular Endothelial Growth Factor Secretion from Pituitary Folliculostellate Cells: Role of K ATP Channels
Author(s) -
Budzik J.,
Omer S.,
Morris J. F.,
Christian H. C.
Publication year - 2014
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12117
Subject(s) - medicine , endocrinology , secretion , biology , vascular endothelial growth factor , pituitary adenylate cyclase activating peptide , activator (genetics) , angiogenesis , neuropeptide , receptor , vasoactive intestinal peptide , vegf receptors
Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen responsible for physiological and pathological angiogenesis. Abnormal regulation of VEGF expression in anterior pituitary folliculostellate ( FS ) cells has been implicated in pituitary tumour progression. FS and endocrine cells express VEGF , which is considered to be secreted by the constitutive pathway. The present study investigated the mechanism of VEGF secretion in TtT/ GF cells, a mouse FS cell line. TtT/ GF cells were shown to express VEGF 164 , the most potent and bioavailable isoform of VEGF . Immunofluorescence and immunogold electron microscopy localised VEGF to the cytoplasm and small electron‐lucent vesicles. Pituitary adenylate cyclase‐activating polypeptide (PACAP) , a well‐documented stimulant of VEGF secretion, caused a robust increase in VEGF secretion over 24 h. Glyburide, an ABCA 1 and K ATP channel blocker, also caused an increase in VEGF secretion when applied alone, and amplified the response to PACAP . Other ABCA 1 transport blockers did not affect VEGF secretion. Exposure of TtT/ GF cells to cycloheximide with PACAP or glyburide inhibited the increased secretion of VEGF , consistent with control of secretion at the transcription level. The SUR 2B/Kir6.1 form of K ATP channels was shown to be expressed by TtT/ GF cells. Diazoxide, a K ATP activator, inhibited PACAP ‐ and PACAP + glyburide‐stimulated VEGF secretion but not that of glyburide alone. These data suggest that K ATP channels are expressed by FS cells and play a significant role in the control of VEGF secretion, and also that activation of K ATP channels inhibits the secretion of VEGF at the level of transcription.