In vitro characterization of angiotensin mediated ACTH release

Autor: D O Sobel, R E Johnsonbaugh
Rok vydání: 1981
Předmět:
Zdroj: Pediatric Research. 15:1563-1563
ISSN: 1530-0447
0031-3998
DOI: 10.1203/00006450-198112000-00166
Popis: We recently demonstrated that angiotensin II(AII)directly mediates in vitro ACTH secretion in rat pituitary cells.To investigate the structure activity relationship of the All molecule and intra-cellular events involved in All mediated ACTH release we studied: 1)the ACTH stimulatory activity of the All fragments AII(2-8),AII (3-8)and AII(4-8) 2)the effect of isobutyl-3-methylxanthine(IBMX)an adenyl cyclase inhibitor,prostaglandin E2 (PGE2)and cyproheptadine on All mediated ACTH release.Anterior rat pituitaries were enzymatically dispersed in trypsin/DNAase solution and placed in mono-layer cell cultures.After 3 days of incubation,the cells were washed and incubated for 4 hrs in test media which was later asayed for ACTH by RIA.AII(10nM)elicited a 150-180% increase of ACTH secretion over control cells.A declining ACTH releasing activity was demonstrated with each consecutive C terminal aminoacid deletion from AII.AII with IBMX(1mM)released more ACTH over its control (IBMX alone) than the ACTH released by All over its control(p AII(2-8)>AII (3-8)>AII(4-8).IBMX potentiates,PGE2 inhibits,and cyproheptadine has no effect on AII mediated ACTH release.Thus the C terminal aminoacids of AII are important to its ACTH stimulatory activity.It is suggested that higher intracellular C'AMP sensitized AII mediated ACTH release and PGE2 may be a factor in this process.
Databáze: OpenAIRE