5-Hydroxytryptamine stimulates corticosteroid-sensitive CRF release from cultured foetal hypothalamic cells. Role of protein kinases.

Abstract:

:5-Hydroxytryptamine (5-HT) has been shown to activate the hypothalamo-pituitary-adrenal axis, possibly by a direct action on hypothalamic CRF synthesis and release. In order to study the mechanisms involved in this effect, foetal hypothalamic cells were cultured and corticotropin-releasing factor-41 (CRF) release was measured by radioimmunoassay. 5-HT induced CRF release in a dose-dependent manner. Further studies were performed with a specific protein kinase C inhibitor, H-7 (1-(5-isoquinolinesulfonyl)-2-methyl-piperazine) and a specific cyclic adenosine monophosphate-dependent protein kinase inhibitor, IP-20. Basal release of CRF-41 from the cultured hypothalamic cells was unaffected by IP-20 and was only diminished at a high (50 microM) concentration of H-7. 5-HT stimulated-CRF release, however, was blocked by both H-7 and IP-20. Dexamethasone and aldosterone both caused a dose-dependent inhibition of 5-HT induced CRF release. These results demonstrate that CRF can be released from hypothalamic neurons in response to 5-HT through a protein kinase C and protein kinase A dependent mechanism and that 5-HT stimulated CRF release can be inhibited by dexamethasone and aldosterone.

journal_name

Brain Res

journal_title

Brain research

authors

Hu SB,Lightman SL,Tannahill LA

doi

10.1016/0006-8993(92)90826-u

subject

Has Abstract

pub_date

1992-03-06 00:00:00

pages

266-70

issue

1-2

eissn

0006-8993

issn

1872-6240

pii

0006-8993(92)90826-U

journal_volume

574

pub_type

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