RESUMEN
Histamine is found in developing mammalian brain in both neurons and mast cells. Under normal conditions, histamine H1 and H2 receptors are found in neural, glial and endothelial cells, and H3 receptors at least on neurons. Experimental brain tumors display both H1 and H2 receptors, and histamine increases permeability in the tumors and in the neighboring areas. Many studies have addressed histaminergic signalling mechanisms in cell lines originating from brain tumors. However, the role of histamine in normal development of brain structures, proliferation and differentiation of neurons and glial cells, and growth of malignant tumors in situ is still poorly understood.
Asunto(s)
Neoplasias Encefálicas/metabolismo , Encéfalo/metabolismo , Histamina/metabolismo , Animales , Encéfalo/crecimiento & desarrollo , Humanos , Ratas , Receptores Histamínicos H1/metabolismo , Receptores Histamínicos H2/metabolismo , Receptores Histamínicos H3/metabolismoRESUMEN
1. We have used 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) to investigate autoregulation of homologous receptor and the control of c-myc mRNA and protein expression in C3H/10T1/2 cells. 2. 10 nM 1,25-(OH)2D3 stimulated 1,25-(OH)2D3 receptor (VDR) synthesis in both non-transformed C3H/10T1/2 Cl 8 and in chemically transformed C3H/10T1/2 Cl 16 cells within 4 hr of treatment. Maximal induction was observed between 8 and 24 hr. 3. Two VDR mRNA transcripts, 2.7 and 4.8 kb, were present in both cell types. There were parallel changes in VDR specific mRNA levels and cellular VDR concentration in the C3H/10T1/2 Cl 8 cells indicating that the increase in receptor concentrations was dependent on de novo mRNA synthesis. 4. The increase in VDR mRNA concentration in the chemically transformed C3H/10T1/2 Cl 16 cells was maximal already at 4 hr, preceding the maximal increase in receptor concentration by 4-6 hr. 5. Analysis of c-myc mRNA levels also showed cell line specificity. 6. The c-myc mRNA level increased 2.1-fold with 10 nM 1,25-(OH)2D3 treatment in C3H/10T1/2 Cl 8 cells after 12 hr while the C3H/10T1/2 Cl 16 cells had maximal c-myc mRNA level after 1 hr. 7. The relative amount of c-myc mRNA remained higher than that of unstimulated controls the next 10-12 hr in C3H/10T1/2 Cl 16 cells. 8. The c-myc protein levels were not affected by 1,25-(OH)2D3 treatment in either cell line as detected by Western blot analysis. 9. Our data suggest that 1,25-(OH)2D3 mediated induction of VDR does not require prior c-myc protein synthesis in the C3H/10T1/2 cells.(ABSTRACT TRUNCATED AT 250 WORDS)