RESUMO
In cerebellar slices, the lowering of oxygen availability, obtained by bubbling N(2) in the medium, reduced the incorporation of radioactive serine into phosphatidylserine (PtdSer). CPCCOEt, an antagonist of metabotropic glutamate receptors type 1 (mGluR1) counteracted the effect, whereas antagonists of NMDA or AMPA receptors were ineffective. In oxygenated slices, agonists of Group I mGluRs, which include mGluR1, inhibited PtdSer synthesis. This effect was also counteracted by CPCCOEt. These findings indicate that glutamate inhibits PtdSer synthesis by acting on mGluR1. This could be important in relation to the known release of glutamate in hypoxia-ischaemia conditions. In cerebellar Purkinje cells, mGluR1 are involved in the generation of mGluR-EPSP evoked by parallel fibre stimulation. The administration of l-serine to cerebellar slices reduced in a dose-dependent manner the mGluR-EPSP evoked by parallel fibre stimulation. The effect was mostly due to the increased synthesis of PtdSer. Thus inhibition of PtdSer synthesis, mediated by mGluR1, may participate in the generation of mGluR-EPSP.
Assuntos
Isquemia Encefálica/metabolismo , Cerebelo/metabolismo , Fosfatidilserinas/biossíntese , Receptores de Glutamato Metabotrópico/fisiologia , Animais , Hipóxia Celular/fisiologia , Cerebelo/efeitos dos fármacos , Estimulação Elétrica , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Técnicas In Vitro , Masculino , Ratos , Receptores de Glutamato Metabotrópico/agonistas , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Receptores de Glutamato Metabotrópico/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/metabolismo , Serina/metabolismo , Serina/farmacologiaRESUMO
Group B streptococcus (GBS) induced macrophage apoptosis by which it could avoid host defence mechanisms. Macrophages, which constitutively express phosphatidylserine (PtdSer) on the outer leaflet of plasma membrane, increased PtdSer exposure during GBS-induced apoptosis. Induction of apoptosis decreased PtdSer radioactivity of macrophages incubated with [(3)H]serine. The effect appeared not due to increasing conversion of PtdSer to phosphatidylethanolamine or phosphatidylcholine nor to the release of radioactive membrane vesicles. The radioactivity in lysoPtdSer was also reduced. These results confirm that induction of apoptosis involves a modification of PtdSer metabolism and point out the typical features of the GBS-induced apoptosis with respect to other models of apoptosis.
