Mitogen-stimulated glucose transport in thymocytes. Possible role of Ca++ and antagonism by adenosine 3':5'-monophosphate.

Abstract

The plant lectin, concanavalin A (Con-A), and the ionophore, A-23187 (specific for divalent cations), stimulated glucose transport in rat thymocytes. Con-A stimulation developed more slowly and was somewhat less extensive than that of A-23187. Both responses showed saturation dose dependencies. The two responses were poorly additive, suggesting that A-23187 may saturate regulatory processes shared by the two stimulatory mechanisms.Doses of methylisobutylxanthine (MIX) and prostaglandin Ez which raised adenosine 3' :5'-monophosphate (cAMP) levels in these cells also antagonized the Con-A stimulation of glucose transport but did not inhibit basal glucose transport or the A-23187 stimulation. Dibutyryl-cAMP and 8-bromo-cAMP also antagonized Con-A stimulation without inhibiting basal glucose transport. MIX antagonized high Con-A doses about as strongly as it did low Con-A doses, suggesting that MIX did not compete in the Con-A binding step or other process saturable by Con-A. [3H]Con-A binding was not affected by MIX.The stimulatory effects of Con-A and A-23187 were reduced by reduction of Ca ++ in the medium. Both Con-A and A-23187 enhanced 45Ca § influx and cellular Ca § content. The A-23187 dose, which was saturating for glucose transport stimulation, enhanced Ca ++ influx and cellular Ca ++ content more than did the Con-A dose which was saturating for glucose transport stimulation. The dose of MIX which specifically antagonized Con-A stimulation of glucose transport proved also to reduce Ca ++ influx and cellular Ca ++ in the presence of Con-A but not in the presence of A-23187. Thus, glucose transport correlates rather well with cellular Ca ++ .These results are compatible with the view that Ca ++ in a cellular compartment can promote glucose transport, that Con-A's enhancement of Ca ++ entry contributes to its stimulation of glucose transport, and that MIX antagonizes Con-A action at least partly by reducing Ca ++ entry. The action of MIX is apparently mediated by cAMP. 456

Effects of tri-n-butyltin chloride on energy metabolism, macromolecular synthesis, precursor uptake and cyclic AMP production in isolated rat thymocytes

“…When cells were incubated in the presence of 13-hydroxybutyrate, a concentration-related stimulation was observed. These findings indicate an inverse relationship between the cellular energy state and 3-O-methylglucose transport, as was described previously for the effects of anoxia, respiratory inhibitors and uncouplers on avian erythrocytes [28] and rat thymocytes [29].…”

“…Consistent with this assumption is the lack of effects on amino acid transport, since the uptake of AIB or lysine could not be inhibited by high concentrations (1 mM or more) of energy poisons such as 2,4 dinitrophenol (2,4-DNP), cyanide or iodoacetate in reticulocytes or a lymphocytic cell line [34,35]. Increased 3-O-methylglucose uptake is regularly seen upon incubation with inhibitors of energy metabolism [28,29]. Plagemann and co-workers using Novikoff rat hepatoma cells demonstrated that ATP depletion did not affect transport of TdR or Urd, but effectively reduced phosphorylation of these nucleosides in situ, resulting in a decrease in macromolecular synthesis [36][37][38].…”

Studies of the mechanism by which 3,5,3'- triiodothyronine stimulates 2-deoxyglucose uptake in rat thymocytes in vitro. Role of calcium and adenosine 3':5'-monophosphate.

“…Both calcium and cyclic (c) AMP have been implicated in the regulation of the uptake of sugar in various tissues (4)(5)(6)(7)(8)(9)(10). In addition, thyroid hormone has been demonstrated to affect both calcium (11)(12)(13) and cAMP (14)(15)(16)(17)(18) metabolism in different tissues.…”

Stimulation of sugar uptake and thymidine incorporation in mouse 3T3 cells by calcium phosphate and other extracellular particles.

“…3 and 4), this does not rule out the possibility of effects due to free Ca2+, particularly in experiments in which the Ca2+ concentration in the medium is lowered rather than raised above physiological levels (24). Free Ca2+ is stimulatory for both sugar transport (25) and cell growth (26) …”