RESUMEN
The present experiments were performed to determine pathways responsible for arachidonic acid release stimulated by cholecystokinin (CCK) and phorbol ester, 4 beta-phorbol 12-myristate 13-acetate (PMA), and the roles of pathways in the secretory response in dispersed acini from guinea pig pancreas. Both CCK-octapeptide (CCK-OP) and PMA increased intracellular arachidonic acid. To determine the source of released arachidonic acid, we measured the effects of PMA and CCK-OP on cellular 1,2-diacylglycerol and lysophosphatidylcholine (LPC) and of diglyceride lipase inhibitor RHC 80267 on [3H]arachidonic acid release. Both PMA and CCK-OP increased 1,2-diacylglycerol and LPC. RHC 80267 had no effect on LPC but inhibited the increase in [3H]arachidonic acid release with a concentration of CCK-OP that was maximal for enzyme secretion. The increase in [3H]arachidonic acid release with PMA or a supramaximal concentration of CCK-OP was not inhibited by RHC 80267. In parallel fashion, RHC 80267 inhibited amylase release caused by maximally effective concentrations of CCK-OP but not that caused by PMA or by supramaximally effective concentrations of CCK-OP. Arachidonic acid stimulated amylase release. Exogenous addition of phospholipase A2 caused increases in [3H]arachidonic acid release, LPC formation, and amylase release. The results indicate that there are at least two pathways responsible for the increase in free cellular arachidonic acid stimulated by pancreatic agonists. One is sequential action of phospholipase C and diglyceride lipase on phosphatidylinositol. The other is a phospholipase A action on phosphatidylcholine. The results also suggest a stimulatory role for both pathways in the secretory response.
Asunto(s)
Amilasas/metabolismo , Ácidos Araquidónicos/metabolismo , Páncreas/metabolismo , Sincalida/farmacología , Acetato de Tetradecanoilforbol/farmacología , Animales , Ciclohexanonas/farmacología , Diglicéridos/metabolismo , Ácidos Grasos/análisis , Cobayas , Técnicas In Vitro , Cinética , Lipoproteína Lipasa/antagonistas & inhibidores , Lisofosfatidilcolinas/aislamiento & purificación , Lisofosfatidilcolinas/metabolismo , Lisofosfatidilcolinas/farmacología , Páncreas/citología , Páncreas/efectos de los fármacos , Fosfatidilcolinas/aislamiento & purificación , Fosfatidilcolinas/metabolismo , Fosfolipasas A/farmacología , Fosfolipasas A2RESUMEN
During first 3 days after mice irradiation and syngeneic bone marrow transplantation in them the number of CFUs (about 0,5% of the injected cells) was stable, although the proliferation induction began 24 hours after transplantation. As it was shown by the method of "thymidine self-distruction". Twenty four hours later all the CFUs entered the mitotic cycle. On the contrary, the commited cells (granulopoesis precursors) compartment (CFUc) enters the logarithmic growth phase since the first day. The exponential growth of the CFUs number was observed from the 4th day simultaneously with the increasing of the proliferation rate of CFUc and the beginning of the recovery of the bone marrow cells total number. In late radiation chimeras (1 month after radiation and reconstitution) the total number of CFUs was 50--70% of the initial. The other hemopoetic parameters were in the normal limits.
Asunto(s)
Sistema Hematopoyético/efectos de la radiación , Quimera por Radiación , Animales , Células de la Médula Ósea , Trasplante de Médula Ósea , División Celular/efectos de la radiación , Radioisótopos de Cesio , Femenino , Granulocitos/efectos de la radiación , Células Madre Hematopoyéticas/efectos de la radiación , Cinética , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Factores de Tiempo , Trasplante IsogénicoRESUMEN
After a sublethal (200 rad) irradiation of mice there occurred during the first 24 hours in the bone marrow a marked reduction of the number of the stem (to 4%), committed precursors of granulocytes and macrophages (to 20%) and of the morphologically-identified cells (to 50%). Complete restoration of hemopoiesis was observed by the end of the 2 weeks after the irradiation and was primarily due to the exponential growth of the number of the stem cells and their intensified proliferation. An increase in the number of the committed precursors was retarded to the moment of restoration of the normal amount of cells in the bone marrow.