Effects of antiglaucoma drugs on [32P]orthophosphate incorporation into phospholipids of cat iris and ciliary process.
The effects of antiglaucoma drugs on [32P]-orthophosphate incorporation into phospholipids of iris and ciliary process were investigated. Both iris and ciliary process rapidly incorporated 32Pi into the major phospholipids, with the acidic phosphoinositides demonstrating a greater labelling than phosphatidylcholine, indicating a greater turnover. The muscarinic agonists, carbachol and pilocarpine, stimulated 32Pi-labelling of phosphatidylinositol (PI) and phosphatidic acid (PA) in both iris and ciliary process. These effects were blocked by atropine, suggesting that the response was mediated through muscarinic receptors. The beta blocking ocular hypotensive drugs, propranolol, timolol and atenolol, produced varying effects on 32P incorporation into phospholipids of iris and ciliary process. Propranolol stimulated 32Pi-labelling into phosphatidylinositol 4', 5' bisphosphate (PIP2), phosphatidylinositol 4' phosphate (PIP), PI and PA. Timolol decreased 32Pi-incorporation into PIP2 and PI, whereas atenolol, a selective beta 1 antagonist, had no significant effect on 32Pi-labelling of phospholipids. The above findings on propranolol agree with previous observations which demonstrated that propranolol redirects glycerolipid metabolism through multiple effects on the enzymes in phospholipid biosynthesis, particularly in stimulating phosphatidylinositol kinases. The results with timolol suggest that this drug may decrease phosphoinositide hydrolysis. The effects of these ocular hypotensive, non-selective beta blocking drugs on phospholipid turnover may ultimately limit the accumulation of breakdown products which could serve as cellular messengers.
D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002415:Cats; D002924:Ciliary Body / Q000187:drug effects*; D007429:Intraocular Pressure / Q000187:drug effects*; D007498:Iris / Q000187:drug effects*; D010710:Phosphates / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D010862:Pilocarpine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013999:Timolol / Q000494:pharmacology
D010710:Phosphates; D010743:Phospholipids; D010862:Pilocarpine; D001262:Atenolol; D013999:Timolol; D002217:Carbachol; D011433:Propranolol