TY - JOUR
T1 - Cyclic GMP metabolism in macrophages. I. Regulation of cyclic GMP levels by calcium and stimulation of cyclic GMP synthesis by NO-generating agents
AU - Bromberg, Yael
AU - Pick, Edgar
N1 - Funding Information:
I This work was supported by a grant from the Leukemia Research Foundation, Inc., Chicago, Illinois, and by Grant 1505 from the U.S.-Israel Binational Science Foundation. * Author to whom reprint requests should be addressed.
PY - 1980/6
Y1 - 1980/6
N2 - Levels of guanosine 3′,5′-cyclic monophosphate (cGMP) were determined by radioimmunoassay in adherence-purified, oil-induced guinea pig peritoneal exudate macrophages, after extraction of the cells with perchloric acid, purification on Dowex AG1-X8, and acetylation. We found that: (i) Basal cGMP levels were strictly dependent on the concentration of extracellular Ca2+ (0.33 ± 0.03 pmol/mg macrophage protein in Ca2+-free medium and 2.49 ± 0.42 pmol/mg in 1.8 mM Ca2+). (ii) The stimulatory effect of Ca2+ on cGMP levels was prevented by tetracaine. (iii) The cGMP content of macrophages was not elevated by incubation with the ionophore A23187 at extracellular Ca2+ concentrations varying between 0 and 1.8 mM. (iv) Macrophage cGMP levels were increased markedly (up to 40-fold) by incubation of the cells with the nitric oxide (NO)-generating agents, sodium azide, hydroxylamine, sodium nitrite, and sodium nitroprusside. (v) Stimulation of cGMP accumulation by NO-generating agents occurred within 30 sec, was Ca2+-independent, and developed in the presence and absence of the phosphodiesterase inhibitor, isobutyl-methylxanthine. (vi) A minimal elevation in the macrophage cGMP level (less than 2-fold) was induced by ascorbic acid but no significant increases were induced by the following agents, found effective in other cells: serotonin, acetylcholine, carbamylcholine, phorbol myristate acetate, arachidonic acid, Superoxide dismutase, and nitrate reductase.
AB - Levels of guanosine 3′,5′-cyclic monophosphate (cGMP) were determined by radioimmunoassay in adherence-purified, oil-induced guinea pig peritoneal exudate macrophages, after extraction of the cells with perchloric acid, purification on Dowex AG1-X8, and acetylation. We found that: (i) Basal cGMP levels were strictly dependent on the concentration of extracellular Ca2+ (0.33 ± 0.03 pmol/mg macrophage protein in Ca2+-free medium and 2.49 ± 0.42 pmol/mg in 1.8 mM Ca2+). (ii) The stimulatory effect of Ca2+ on cGMP levels was prevented by tetracaine. (iii) The cGMP content of macrophages was not elevated by incubation with the ionophore A23187 at extracellular Ca2+ concentrations varying between 0 and 1.8 mM. (iv) Macrophage cGMP levels were increased markedly (up to 40-fold) by incubation of the cells with the nitric oxide (NO)-generating agents, sodium azide, hydroxylamine, sodium nitrite, and sodium nitroprusside. (v) Stimulation of cGMP accumulation by NO-generating agents occurred within 30 sec, was Ca2+-independent, and developed in the presence and absence of the phosphodiesterase inhibitor, isobutyl-methylxanthine. (vi) A minimal elevation in the macrophage cGMP level (less than 2-fold) was induced by ascorbic acid but no significant increases were induced by the following agents, found effective in other cells: serotonin, acetylcholine, carbamylcholine, phorbol myristate acetate, arachidonic acid, Superoxide dismutase, and nitrate reductase.
UR - http://www.scopus.com/inward/record.url?scp=0018859909&partnerID=8YFLogxK
U2 - 10.1016/0008-8749(80)90401-3
DO - 10.1016/0008-8749(80)90401-3
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AN - SCOPUS:0018859909
SN - 0008-8749
VL - 52
SP - 73
EP - 83
JO - Cellular Immunology
JF - Cellular Immunology
IS - 1
ER -
