Platelet activating factor induces inositol phosphate accumulation in cultures of rat and bovine anterior pituitary cells.
The phospholipid platelet-activating factor (PAF) (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) stimulated the accumulation of inositol phosphates in cultures of rat and bovine anterior pituitary cells. In response to PAF, inositol 1,4-bisphosphate showed the largest percent increase of the inositol phosphates in the presence of lithium chloride. PAF induced an increase of inositol 1,4,5-trisphosphate, the biologically active isomer responsible for mobilization of intracellular calcium. A characterization of the PAF response indicated that PAF, but not its biologically inactive enantiomer, induced the accumulation of inositol phosphates in the rat anterior pituitary. Further, the PAF receptor antagonist L652731 reduced PAF stimulation. The ED50 for PAF-induced inositol 1,4-bisphosphate accumulation was 0.4 nM. PAF induced a rapid response that did not persist beyond 20 min. While PAF treatment of anterior pituitary cells did not alter TRH-induced inositol phosphate accumulation, it did prevent a second exposure of PAF from inducing inositol phosphate accumulation. These data suggest that PAF induces a rapid stimulation of phospholipase C causing the hydrolysis of phosphatidylinositol 4,5-bisphosphate and the generation of the second messengers, inositol 1,4,5-trisphosphate and diglyceride, in anterior pituitary tissue. This action is transient probably due to PAF receptor desensitization. The action of PAF on generation of inositol phosphates may account, in part, for PAF-induced secretion of PRL and GH.
Grandison
L
L
University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635.
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D005663:Furans / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D002712:Chlorides; D005663:Furans; D007295:Inositol Phosphates; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; C044259:inositol 1,4-bis(phosphate); D013973:Thyrotropin-Releasing Hormone; D015544:Inositol 1,4,5-Trisphosphate; C047504:2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran; D008094:Lithium; D010738:Type C Phospholipases; D018021:Lithium Chloride