Phloretin as an antagonist of prostaglandin F2 alpha receptor in cultured rat astrocytes.
The effect of phloretin on prostaglandin (PG) F2 alpha-induced phosphoinositide hydrolysis and elevation of intracellular Ca2+ concentration was examined in cultured rat astrocytes. Phloretin inhibited PGF2 alpha (1 microM)-induced phosphoinositide hydrolysis in a concentration-dependent manner with an IC50 value of 16 microM. The inhibitory action of phloretin was specific for PGs. The addition of increasing concentrations of phloretin caused progressive shifts of the dose-response curves of PGF2 alpha to the right. In digitonin-permeabilized astrocytes, phloretin (100 microM) inhibited the stimulation induced by PGF2 alpha (1 microM) plus GTP gamma S (50 microM) without affecting that induced by GTP gamma S alone. PGF2 alpha at 1 microM transiently increased astrocytic intracellular Ca2+ concentration in 39% of the cells tested. The response was completely blocked by 100 microM phloretin and the calcium response recovered again after washing out phloretin. These results suggest that phloretin is an antagonist of PGF2 alpha receptor linked to phospholipase C in astrocytes.
Kitanaka
J
J
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Ishibashi
T
T
Baba
A
A
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007700:Kinetics; D009638:Norepinephrine / Q000494:pharmacology; D010693:Phloretin / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*
D016232:Endothelins; D005971:Glutamates; D010716:Phosphatidylinositols; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D002217:Carbachol; D015237:Dinoprost; D015232:Dinoprostone; D015230:Prostaglandin D2; D010693:Phloretin; D002118:Calcium; D009638:Norepinephrine