Effects of phospholipid vesicles (liposomes) on cAMP levels in the rat cerebral cortex.
We studied the effects of two types of liposomes (cholate-free liposomes and cholate-containing liposomes) on control (in the presence of 3-isobutyl-1 methyl xanthine [IBMX], a phosphodiesterase inhibitor) and stimulated (IBMX plus isoprenaline) cyclic 3',5'-adenosine monophosphate (cAMP) accumulation in slices of rat cerebral cortex. Our purpose was to examine whether or not liposomes with different lipid constituents modify levels of cAMP in vitro. Liposomes at low concentrations had a significant inhibitory effect on cAMP accumulation in brain tissue. This inhibition was concentration-dependent. Cholate-containing liposomes had a greater inhibitory effect at higher concentrations. Liposomes also inhibited cAMP accumulation in a dose-dependent manner when the tissues were preincubated with ouabain, a Na(+)-K(+)-ATPase inhibitor. These results demonstrate that, in rat brain, liposomes alone modified important biochemical responses such as the adenylyl cyclase-cAMP system coupled to beta-adrenoceptors. The significance of these findings for the mechanism of the action of liposomes is discussed.
Mármol
F
F
Unitat de Farmacologia, Terapèutica i Farmacologia Clínica, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain. marmol@medicina.ub.es
Gonzalez
P
P
Maierhofer
G
G
Gimenez
J
J
Forn
J
J
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005765:Gastrointestinal Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008081:Liposomes / Q000494:pharmacology*; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020358:Sodium Cholate / Q000494:pharmacology; D012995:Solubility
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D005765:Gastrointestinal Agents; D008081:Liposomes; D010726:Phosphodiesterase Inhibitors; D010042:Ouabain; D000242:Cyclic AMP; D007545:Isoproterenol; D020358:Sodium Cholate; D015056:1-Methyl-3-isobutylxanthine