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2.
J Cell Physiol ; 149(3): 403-7, 1991 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-1835980

RESUMEN

In RBL-2H3 rat leukemic mast cells, cross-linking anti-DNP IgE-receptor complexes with multivalent antigen (DNP-BSA) activates a signal transduction pathway leading to Ca2+ influx and secretion. Cross-linking IgE-receptor complexes also stimulates a pathway that inactivates (desensitizes) receptors; this pathway becomes important at high concentrations of cross-linking antigen. Recent evidence that antigen-induced secretion is impaired by mycophenolic acid (MPA), an inhibitor of guanine nucleotide synthesis de novo, has implicated a GTP-binding protein (G protein) in the signaling pathway. Other recent studies have indicated that the conversion of cross-linked receptors to a detergent-insoluble (cytoskeleton-associated) form at high antigen concentrations is correlated with the loss of signaling activity. Here we show that secretion elicited by an optimal concentration of antigen (0.05 micrograms/ml DNP-BSA) is only inhibited by about 25% in guanine nucleotide-depleted cells, whereas secretion elicited by 5 micrograms/ml DNP-BSA, a concentration in the range that causes the high-dose inhibition of secretion, is inhibited by more than 60%. We also show that IgE-receptor complexes are insolubilized in response to 5 but not 0.05 micrograms/ml DNP-BSA in both control and guanine nucleotide-depleted cells. Importantly, the extent of insolubilization elicited by 5 micrograms/ml DNP-BSA is increased by more than 60% in the guanine nucleotide-depleted samples. These results raise the possibility that guanine nucleotide depletion reduces the secretory response to high antigen concentrations in two ways: by inhibiting the G protein-coupled signaling pathway and by increasing the availability of receptors to the pathway leading to receptor insolubilization and inactivation.


Asunto(s)
Antígenos de Diferenciación de Linfocitos B/metabolismo , Nucleótidos de Guanina/biosíntesis , Ácido Micofenólico/farmacología , Receptores Fc/metabolismo , Animales , Antígenos de Diferenciación de Linfocitos B/efectos de los fármacos , Calcio/metabolismo , Línea Celular , Dinitrofenoles/farmacología , Inmunoglobulina E/metabolismo , Cinética , Mastocitos , Ratas , Receptores Fc/efectos de los fármacos , Receptores de IgE , Albúmina Sérica Bovina/farmacología , Transducción de Señal/efectos de los fármacos
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