An analogue of creatine increases TRH-stimulated prolactin secretion and phosphoinositide hydrolysis in rat pituitary tumor cells.
Prolactin (PRL)-secreting GH3 cells were grown, in vitro, with the creatine analogue beta-guanidinopropionic acid (GPA) added to the culture medium. After 5 days there was a small increase in basal and greatly increased thyrotropin-releasing hormone (TRH)-stimulated PRL secretion. The site of action of GPA is at the TRH-induced hydrolysis of phosphoinositides, since increased amounts of mono, bis and tris/tetrakis inositol phosphates were found in treated cells, while the PRL secretion induced by a phorbol ester or a calcium ionophore, treatments which mimic the second messages generated by inositol phospholipid hydrolysis, were not enhanced by GPA. The mechanism by which GPA increases phospholipase C activity has not been fully elucidated but may involve the activity of a controlling G protein.
Prysor-Jones
R A
RA
Department of Medicine, St. George's Hospital Medical School, London, U.K.
Silverlight
J J
JJ
Whitley
G S
GS
Jenkins
J S
JS
D000634:Aminoquinolines; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D003401:Creatine / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000096:biosynthesis; D007773:Lactates / Q000096:biosynthesis; D008094:Lithium / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010725:Phosphocreatine / Q000502:physiology; D010911:Pituitary Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D000634:Aminoquinolines; D006146:Guanidines; D007295:Inositol Phosphates; D007773:Lactates; D010716:Phosphatidylinositols; D011422:Propionates; D010725:Phosphocreatine; D000001:Calcimycin; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D008094:Lithium; D003401:Creatine; D013755:Tetradecanoylphorbol Acetate; C035739:Quin2; C005775:guanidinopropionic acid