Cationic amphiphilic drugs perturb the metabolism of inosititides and phosphatidic acid in photoreceptor membranes.
Incubation of purified bovine photoreceptor rod outer segments with [gamma-32P]ATP resulted in the labeling of phosphatidylinositol 4-phosphate (PIP) and phosphatidic acid (PA) with little labeling of phosphatidylinositol 4,5-bisphosphate (PIP2). Propranolol inhibited in a dose-dependent manner the labeling of PA and enhanced that of PIP. Various cationic amphiphilic drugs also were tested for these effects. Propranolol had the same effects on high-speed rat brain particulate material. While this particular preparation displayed more labeling of PIP2, propranolol was ineffective, as it was on retinal PIP-kinase. Ca2+-activated polyphosphoinositide phosphodiesterase activity in nerve-ending membranes also was inhibited by propranolol. It is concluded that cationic amphiphilic drugs can inhibit diacylglycerol kinase and the polyphosphoinositide phosphodiesterase and stimulate the phosphatidylinositol-kinase (but not PIP-kinase).
D000081:Acetamides / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002738:Chloroquine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008012:Lidocaine / Q000494:pharmacology; D008027:Light; D008274:Magnesium / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor); D010786:Photoreceptor Cells / Q000187:drug effects*; D011343:Procaine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D012160:Retina / Q000201:enzymology; D012374:Rod Cell Outer Segment / Q000187:drug effects* / Q000378:metabolism; D013748:Tetracaine / Q000494:pharmacology
D000081:Acetamides; D010712:Phosphatidic Acids; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C037178:phosphatidylinositol 4-phosphate; D013748:Tetracaine; D011343:Procaine; D002738:Chloroquine; D000255:Adenosine Triphosphate; D008012:Lidocaine; D011433:Propranolol; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D008274:Magnesium; D002118:Calcium; C038931:cetamolol