title: Modulatory effects of phosphatidylserine on the binding of muscarinic cholinergic receptor ligands. Studies in vitro and in vivo.
abstract: The modulation of the binding of muscarinic cholinergic receptor ligands by phosphatidylserine purified from bovine cerebral cortex (BC-PS) was examined in vitro and in vivo. The enrichment of bovine cerebral cortical synaptosomal membranes with BC-PS, using a fusion technique, produced a concentration-dependent decrease in the affinity (increase in Kd) of [3H]quinuclidinyl benzylate (3H-QNB) specific binding to muscarinic acetylcholine receptors (mAChR), without changes in their maximal number (Bmax). Similar results were observed when [3H]oxotremorine (3H-OXO) was used to label a high affinity subpopulation of mAChR. On the other hand, preincubation of BC-PS liposomes with synaptosomal membranes in a nonoptimum fusion condition (at pH 7.4) did not alter the binding properties of both radioligands. Fusion experiments using a pure phosphatidylserine preparation from spinal cord revealed a similar decrement in the affinity of 3H-QNB specific binding. Five day's intraperitoneal (i.p.) administration of 15 mg/kg of BC-PS liposomes in rats increased the maximal number of cerebral cortical binding sites for 3H-OXO. Scatchard analysis revealed no changes in the apparent dissociation constant. This modification is selective in relation to the neural structure studied. Thus, BC-PS treatment did not modify 3H-OXO binding in the hippocampal formation and cerebellum. In contrast, parallel experiments using the muscarinic antagonist 3H-QNB showed no alteration in the binding properties of mAChR. Five day's i.p. administration of 15 mg/kg/d of phosphatidylcholine from bovine cerebral cortex (BC-PC) liposomes produced quite similar results to those obtained with BC-PS. These results indicate that mAChR are under the modulatory action of phosphatidylserine (PS) and phosphatidylcholine (PC), and suggest that this endogenous phospholipids may play a regulatory role on the mAChR. The possible implications of these findings on the effects of PC or PS treatment in neurological disorders involving a decrease in central cholinergic functions are discussed.
authors.affiliation: Instituto de Biologia Celular, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: S
authors.initials: S
authors.lastname: Raskovsky
authors.forename: E
authors.initials: E
authors.lastname: Rivas
authors.forename: D
authors.initials: D
authors.lastname: Bernik
authors.forename: J
authors.initials: J
authors.lastname: Medina
authors.forename: D
authors.initials: D
authors.lastname: Jerusalinsky
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D002540:Cerebral Cortex / Q000737:chemistry; D008024:Ligands; D008081:Liposomes; D008561:Membrane Fusion; D010095:Oxotremorine / Q000378:metabolism; D010713:Phosphatidylcholines / Q000494:pharmacology; D010718:Phosphatidylserines / Q000302:isolation & purification / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000737:chemistry; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D008024:Ligands; D008081:Liposomes; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D011976:Receptors, Muscarinic; D010095:Oxotremorine; D011813:Quinuclidinyl Benzilate