RESUMO
Histamine-induced cyclic AMP (cAMP) accumulation was studied in purified primary cultures of type-1 and type-2 astrocytes from neonatal rat brain. Histamine induced remarkable cAMP accumulation in type-1 astrocytes in a dose-dependent manner (EC50 = 1.2 x 10(-5) M, Emax = 1100% of control). In contrast, histamine had no significant effect on cAMP accumulation in type-2 astrocytes. Famotidine, an H2-antagonist, dose-dependently inhibited histamine-induced cAMP accumulation in type-1 astrocytes (Ki = 3 x 10(-8) M), but mepyramine (10(-6) M), an H1-antagonist, had no effect. Dimaprit and impromidine, H2-agonists, stimulated cAMP accumulation, but 2-pyridylethylamine, an H1-agonist, did not stimulate it nor augment the H2-agonist-induced cAMP accumulation. These results indicate that (1) histamine induces cAMP accumulation in type-1 astrocytes but not in type-2 astrocytes, and that (2) histamine-induced cAMP accumulation in type-1 astrocytes is mediated by H2-receptors without significant augmentation via H1-receptors.
Assuntos
Astrócitos/metabolismo , AMP Cíclico/metabolismo , Histamina/farmacologia , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Células Cultivadas , Famotidina/farmacologia , Cinética , Pirilamina/farmacologia , Ratos , Ratos Endogâmicos , Receptores Histamínicos H2/fisiologia , Estimulação QuímicaRESUMO
Histamine elicited dose-dependent accumulation of [3H]inositol phosphates in type-2 astrocytes, but not in type-1 astrocytes. The ED50 was about 2.4 x 10(-6) M and the maximal response was obtained at 10(-4) M. This response was dose-dependently inhibited by H1-antagonists, mepyramine and D- and L-chlorpheniramine. Furthermore, D- and L-chlorpheniramine showed stereoselectivity in the inhibition. On the other hand, an H2-antagonist, famotidine, and an H3-antagonist, thioperamide, did not inhibit the response. These results indicate that histamine stimulates accumulation of inositol phosphates in type-2 astrocytes via H1-receptors.
Assuntos
Astrócitos/metabolismo , Histamina/farmacologia , Fosfatos de Inositol/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Células Cultivadas , Clorfeniramina/farmacologia , Famotidina/farmacologia , Piperidinas/farmacologia , Pirilamina/farmacologia , Ratos , Ratos Endogâmicos , Receptores Histamínicos/metabolismoRESUMO
Liver tissues of 223 autopsy cases of cirrhosis and hepatocellular carcinoma were examined for liver cell dysplasia in relation to hepatitis B surface antigen (HBsAg) detected with orcein stain. Liver cell dysplasia was found in 94 cases (42.2%): 37 were from cases of cirrhosis only, and 53 were from cases of cirrhosis with hepatocellular carcinoma. There was a significant difference in the overall incidence of HBsAg in cases with and without dysplasia (70.2%:32.6%). A similar difference was found in all groups, i.e., those with cirrhosis, cirrhosis with hepatocellular carcinoma, and hepatocellular carcinoma only, in which none of 11 cases of HBsAg negative had dysplasia. A good correlation was seen between the semiquantitative grade of dysplasia and the incidence of HBsAg. These findings suggest a close relationship of HBsAg with liver cell dysplasia.