Calcium-dependent hormonal regulation of amino acid transport and cyclic AMP accumulation in rat hepatocyte monolayer cultures.

Publisher Website
Google Scholar
Abstract
The effect of glucagon, epinephrine, norepinephrine, dexamethasone, insulin and dexamethasone plus glucagon on the transport of 2-aminoisobutyric acid (AIB), and that of glucagon on the production of cAMP, were examined in rat hepatocyte monolayer cultures under 3 different culture conditions involving Ca. The hepatocytes were studied in Ca-containing medium after treatment with or without 0.033% dimethyl sulfoxide, the solvent for the Ca ionophore A23187 (Ca controls); Ca-free medium after treatment with A23187 (Ca-depleted); and Ca-containing medium after treatment with ionophore (Ca-restored). The basal and hormonally regulated rates of AIB transport for hepatocytes in Ca control and Ca-depleted cultures were comparable. The restoration of Ca in Ca-restored cultures increased the basal and the hormonally stimulated transport of AIB when compared to the other conditions. Ca markedly enhanced the stimulation of AIB transport in cultures treated with glucagon, catecholamines and dexamethasone plus glucagon. The level of cAMP production in response to glucagon in Ca control and Ca-depleted cultures was the same and it was conspicuously higher than the level in Ca-restored cultures. Varying the concentration of Ca in the medium used to maintain the hepatocytes in Ca control cultures did not affect the stimulation of AIB transport or cAMP production by glucagon. In Ca-restored cultures, increasing the Ca concentration of the medium resulted in increased stimulation of AIB transport and decreased production of cAMP by glucagon. In the Ca-restored cultures, Ca in the absence of glucagon enhanced AIB transport but had no effect on cAMP production. Cultures maintained for 6 h in Ca-free medium after the depletion of Ca showed a 6- to 7-fold increase in the production of cAMP in response to glucagon, but no stimulation of AIB transport. Apparently mobilization of cellular Ca by glucagon, eiher directly or through cAMP, mediates its stimulation of amino acid transport.