Phorbol ester effects on hormonal responses in freshly isolated short-term incubated and cultured hepatocytes.

Abstract:

:Beta-adrenergic, alpha-1-adrenergic and glucagon stimulation of glucose release were compared between hepatocytes which were freshly isolated, incubated for 3 h in suspension or cultivated for 4 or 24 h in plastic culture flasks in the presence and absence of the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA). In contrast to the absence of an isoproterenol effect in freshly isolated hepatocytes, an increased sensitivity of glucose liberation towards isoproterenol could be observed 4 h after the start of culture, whereas the beta-receptor number was not found to be increased before 24 h. TPA has no effect on isoproterenol-stimulated glucose release at all investigated conditions. The alpha-1-adrenergic responses tested by using the alpha-1-adrenergic agonist phenylephrine is blocked completely in freshly isolated hepatocytes preincubated with 10(-6) M TPA. However, after 3 h incubation of hepatocytes in suspension or in primary culture, TPA had no effect on phenylephrine-stimulated glucose release. The effect of 10(-9) M glucagon on glucose release from freshly isolated hepatocytes was not influenced by TPA, whereas after 90 and 180 min incubation a significant decrease could be observed. On the other hand, TPA inhibited stimulation of adenylate cyclase activity by glucagon concentrations of 10(-5) M in freshly isolated hepatocytes, but no effect was found in hepatocytes incubated for 3 h in suspension or maintained for 24 h in primary culture. The different TPA effects may be an expression of changes of the accessibility of protein kinase C to TPA caused by translocation and/or intracellular activation of this enzyme at the tested experimental conditions.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Hermsdorf T,Dettmer D

doi

10.1016/0898-6568(92)90051-9

subject

Has Abstract

pub_date

1992-11-01 00:00:00

pages

709-14

issue

6

eissn

0898-6568

issn

1873-3913

pii

0898-6568(92)90051-9

journal_volume

4

pub_type

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