RT Journal Article
SR Electronic
T1 Bicarbonate induces sensitization of cyclic AMP accumulation by intact 1321N1 human astrocytoma cells.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1211
OP 1217
VO 264
IS 3
A1 M L Toews
A1 L J Arneson-Rotert
A1 S A Liewer
YR 1993
UL http://jpet.aspetjournals.org/content/264/3/1211.abstract
AB Preincubation of 1321N1 human astrocytoma cells in medium buffered with bicarbonate induced 50 to 100% increases in subsequent stimulation of cyclic AMP accumulation by the beta adrenergic receptor agonist isoproterenol and by the direct adenylyl cyclase activator forskolin, compared to cells incubated in buffered medium without bicarbonate. This "bicarbonate-induced sensitization" of cyclic AMP accumulation occurred rapidly, was rapidly reversible and was bicarbonate concentration-dependent. Although protein kinase C activation also induces sensitization in these cells, sensitization by bicarbonate does not appear to involve protein kinase C, because neither protein kinase C down-regulation nor the kinase inhibitor staurosporine prevented sensitization. Pertussis toxin neither mimicked nor prevented the sensitization by bicarbonate, suggesting that pertussis toxin-sensitive guanine nucleotide-binding proteins are not involved. The effect of bicarbonate appears to be on synthesis of cyclic AMP rather than degradation, inasmuch as the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine did not prevent expression of sensitization and because cyclic AMP degradation rates were not altered after bicarbonate incubation. However, increased adenylyl cyclase activity was not retained in broken cell preparations from cells incubated with bicarbonate. These results suggest the occurrence of a novel mechanism through which bicarbonate exposure can regulate adenylyl cyclase activity in intact cells.