DOI: 10.1111/j.1471-4159.1987.tb04124.x. Atrial Natriuretic Factors Stimulate Accumulation and Efflux of Cyclic GMP in C6–2B Rat Glioma and PC12 Rat Pheochromocytoma Cell Cultures

Atrial Natriuretic Factors Stimulate Accumulation and Efflux of Cyclic GMP in C6–2B Rat Glioma and PC12 Rat Pheochromocytoma Cell Cultures

10.1111/j.1471-4159.1987.tb04124.x

Crossref journal-article

Wiley

Journal of Neurochemistry (311)

Abstract

Abstract: Atrial natriuretic factors (ANFs) were tested for their effects on cyclic GMP production in two neurally derived cell lines, the C6–2B rat glioma cells and the PC12 rat pheochromocytoma cells. These cell lines were selected because both are known to possess high amounts of the particulate form of guanylate cyclase, a proposed target of ANF in peripheral organs. Previous studies from our laboratory have shown that ANF selectively activates paniculate, but not soluble, guanylate cyclase in homogenates of a variety of rat tissues and that one class of ANF receptor appears to be the same glycoprotein as particulate guanylate cyclase. In the present study we found that four analogs of ANF stimulate cyclic GMP accumulation in both C6–2B and PC12 cells with the rank order of potency being atriopeptin HI = atriopeptin II ≥ human atrial natriuretic polypeptide ≥ atriopeptin I. Atriopeptin II (100 nM) for 20 min elevated cyclic GMP content in C6–2B cells fourfold and in PC12 cells 12‐fold. Atriopeptin II (100 nM) for 20 min also stimulated the efflux of cyclic GMP from both C6–2B cells (47‐fold) and PC12 cells (12‐fold). Accumulation of cyclic GMP in both cells and media was enhanced by preincubation with the phosphodiesterase inhibitor 3‐isobutyl‐1‐methylxanthine (250 μM). After 20 min of exposure to atriopeptin II, cyclic GMP amounts in the media were equal to or greater than the amounts in the cells. Although the function of cyclic GMP in neural tissue is at present unclear, the cyclic GMP response observed in C6–2B and PC12 cells may provide important clues concerning the molecular mechanisms of action of ANF in the central and peripheral nervous systems. Since a significant amount of the generated cyclic GMP is released from these cells in response to ANF, extracellular as well as intracellular cyclic GMP may be important in mediating the actions of ANF in neural tissues.

Bibliography

Fiscus, R. R., Robles, B. T., Waldman, S. A., & Murad, F. (1987). Atrial Natriuretic Factors Stimulate Accumulation and Efflux of Cyclic GMP in C6â2B Rat Glioma and PC12 Rat Pheochromocytoma Cell Cultures. Journal of Neurochemistry, 48(2), 522â528. Portico.

Authors 4

Ronald R. Fiscus (first)
Beemeth T. Robles (additional)
Scott A. Waldman (additional)
Ferid Murad (additional)

References 35 Referenced 42

10.1016/S0021-9258(18)34495-8 / J. Biol. Chem. / Alterations of glial tumor cell Ca2+ metabolism and Ca2+‐dependent cAMP accumulation by phorbol myristate acetate by Brostrom M. A. (1982)
10.1126/science.2932797
10.1016/0304-4165(84)90036-9
{'key': 'e_1_2_2_5_1', 'first-page': '415', 'article-title': 'Endothelium‐dependent and nitrovasodilator‐induced activation of cyclic GMP‐dependent protein kinase in rat aorta', 'volume': '9', 'author': 'Fiscus R. R.', 'year': '1983', 'journal-title': 'J. Cyclic Nucleotide Res.'} / J. Cyclic Nucleotide Res. / Endothelium‐dependent and nitrovasodilator‐induced activation of cyclic GMP‐dependent protein kinase in rat aorta by Fiscus R. R. (1983)
10.1016/0167-4889(85)90124-7
10.1016/0014-2999(85)90126-8
10.1016/0006-291X(84)90260-2
{'key': 'e_1_2_2_9_1', 'first-page': '207', 'article-title': 'Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2′O acetylation by acetic anhydride in aqueous solution', 'volume': '1', 'author': 'Harper J. R.', 'year': '1975', 'journal-title': 'J. Cyclic Nucleotide Res.'} / J. Cyclic Nucleotide Res. / Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2′O acetylation by acetic anhydride in aqueous solution by Harper J. R. (1975)
10.1016/0024-3205(85)90425-4
10.1126/science.193187
10.1016/S0021-9258(17)38456-9 / J. Biol. Chem. / Co‐purification of an atrial natriuretic factor receptor and paniculate guanylate cyclase from rat lung by Kuno T. (1986)
10.1056/NEJM198511213132106
10.1016/0167-4889(86)90040-6
{'key': 'e_1_2_2_15_1', 'first-page': '285', 'article-title': 'Possible role of cyclic GMP‐dependent protein kinase in vascular smooth muscle function', 'volume': '17', 'author': 'Lincoln T. M.', 'year': '1984', 'journal-title': 'Adv. Cyclic Nucleotide Res.'} / Adv. Cyclic Nucleotide Res. / Possible role of cyclic GMP‐dependent protein kinase in vascular smooth muscle function by Lincoln T. M. (1984)
10.1038/ki.1985.54
{'issue': '3', 'key': 'e_1_2_2_17_1', 'first-page': 'S111', 'article-title': 'Role of cyclic‐GMP in relaxations of vascular smooth muscle', 'volume': '7', 'author': 'Murad F.', 'year': '1985', 'journal-title': 'J. Cardiovasc. Pharmacol.'} / J. Cardiovasc. Pharmacol. / Role of cyclic‐GMP in relaxations of vascular smooth muscle by Murad F. (1985)
10.1073/pnas.81.19.5946
10.1161/01.HYP.7.4.469
10.1111/j.1471-4159.1978.tb07848.x
10.1161/01.HYP.7.2.306
10.1016/0196-9781(84)90183-9
10.1016/0014-2999(86)90651-5
{'key': 'e_1_2_2_24_1', 'first-page': '101', 'article-title': 'The effect of atriopeptin III on membrane potential and intracellular Ca++‐activity in rat glioma cells', 'volume': '4', 'author': 'Reiser G.', 'year': '1985', 'journal-title': 'Regul. Peptides (Suppl)'} / Regul. Peptides (Suppl) / The effect of atriopeptin III on membrane potential and intracellular Ca++‐activity in rat glioma cells by Reiser G. (1985)
10.1210/endo-117-3-1279
10.1126/science.2858127
10.1016/S0006-291X(85)80179-0
{'key': 'e_1_2_2_28_1', 'first-page': '305', 'volume-title': 'Handbook of Experimental Pharmacology, Vol. 58/II: Cyclic Nucleotide II. Physiology and Pharmacology', 'author': 'Siggins G. R.', 'year': '1982'} / Handbook of Experimental Pharmacology, Vol. 58/II: Cyclic Nucleotide II. Physiology and Pharmacology by Siggins G. R. (1982)
{'key': 'e_1_2_2_29_1', 'first-page': '900', 'article-title': 'Determination of the subcellular distribution of guanylate cyclase in neural crest derived cultured cells using a tandem double monoclonal antibody immunoassay', 'volume': '42', 'author': 'Sinacore M. S.', 'year': '1983', 'journal-title': 'Fed. Proc.'} / Fed. Proc. / Determination of the subcellular distribution of guanylate cyclase in neural crest derived cultured cells using a tandem double monoclonal antibody immunoassay by Sinacore M. S. (1983)
{'key': 'e_1_2_2_30_1', 'first-page': '1114', 'article-title': 'Radioimmunoassay for cyclic nucleotides. II. Adenosine 3′,5′‐monophosphate and guanosine 3′,5′‐monophosphate in mammalian tissue and body fluids', 'volume': '247', 'author': 'Steiner A. L.', 'year': '1972', 'journal-title': 'J. Biol. Chem.'} / J. Biol. Chem. / Radioimmunoassay for cyclic nucleotides. II. Adenosine 3′,5′‐monophosphate and guanosine 3′,5′‐monophosphate in mammalian tissue and body fluids by Steiner A. L. (1972)
10.1016/0006-291X(84)91606-1
10.1016/S0021-9258(18)32306-8 / J. Biol. Chem. / Cyclic GMP efflux from liver slices by Tjörnhammar M‐L. (1983)
10.1016/0014-5793(85)81105-4
10.1016/S0021-9258(17)42597-X
10.1016/0167-4889(85)90191-0
10.1073/pnas.81.23.7661

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 3:58 p.m.)
Deposited	1 year, 10 months ago (Oct. 20, 2023, 10:13 a.m.)
Indexed	1 month ago (July 30, 2025, 10:46 a.m.)
Issued	38 years, 7 months ago (Feb. 1, 1987)
Published	38 years, 7 months ago (Feb. 1, 1987)
Published Online	18 years, 10 months ago (Oct. 5, 2006)
Published Print	38 years, 7 months ago (Feb. 1, 1987)

Funders 0

None

BibTeX

@article{Fiscus_1987, title={Atrial Natriuretic Factors Stimulate Accumulation and Efflux of Cyclic GMP in C6–2B Rat Glioma and PC12 Rat Pheochromocytoma Cell Cultures}, volume={48}, ISSN={1471-4159}, url={http://dx.doi.org/10.1111/j.1471-4159.1987.tb04124.x}, DOI={10.1111/j.1471-4159.1987.tb04124.x}, number={2}, journal={Journal of Neurochemistry}, publisher={Wiley}, author={Fiscus, Ronald R. and Robles, Beemeth T. and Waldman, Scott A. and Murad, Ferid}, year={1987}, month=feb, pages={522–528} }

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