DOI: 10.1111/j.1471-4159.1987.tb03414.x. Ionic Mechanisms Implicated in the Stimulation of Cerebellar Cyclic GMP Levels by <i>N</i>‐Methyl‐D‐Aspartate

Ionic Mechanisms Implicated in the Stimulation of Cerebellar Cyclic GMP Levels by N‐Methyl‐D‐Aspartate

10.1111/j.1471-4159.1987.tb03414.x

Crossref journal-article

Wiley

Journal of Neurochemistry (311)

Abstract

Abstract: N‐Methyl‐D‐aspartate (NMDA) increases cyclic GMP levels in immature rat cerebellar slices incubated in magnesium‐containing Krebs buffer in vitro. This effect is blocked by 2‐amino‐5‐phosphonovalerate and by D‐α‐aminoadipate, but not by glutamic acid diethyl ester or 7–0‐glutamylaminomethylsulfonic acid, indicating specific involvement of the NMDA receptor. The response produced by NMDA is abolished by removal of calcium from the medium, proportional to the concentration of extracellular calcium, and blocked by a number of inorganic (Ni2+, Co2+, Cd2+, La3+, Mn2+) calcium antagonists. The responses to NMDA are not blocked by barium or strontium and persist when these ions are substituted for calcium in the incubation medium. The effects of NMDA are blocked by, but are not particularly sensitive to, the organic voltage‐dependent calcium channel antagonists. Nifedipine (10 μM) produces partial inhibition of the effects of NMDA, which are also antagonized by high (>200 μM) concentrations of diltiazem and verapamil. The effects of NMDA are tetrodotoxin insensitive but are abolished by omission of sodium from the medium and inhibited by a tetrodotoxin‐insensitive sodium channel blocker, Zn2+. The results suggest that calcium channel opening is a consequence of NMDA receptor activation in this model. However, the sodium dependence of the response argues against the use of receptor‐operated calcium channels, whereas the weak activity of the organic voltage‐sensitive calcium channel antagonists argues either against the use of voltage‐dependent calcium channels, or that those implicated in the effects of NMDA are insensitive to these agents. The combined sodium and calcium dependence of the response, and the apparent lack of involvement of either receptor‐operated or voltage‐dependent calcium channels, might alternatively reflect the use of sodium‐dependent calcium influx, initially triggered by NMDA‐induced sodium entry.

Bibliography

Carter, C. J., & Scatton, F. N. B. (1987). Ionic Mechanisms Implicated in the Stimulation of Cerebellar Cyclic GMP Levels by NâMethylâDâAspartate. Journal of Neurochemistry, 49(1), 195â200. Portico.

Authors 2

C. J. Carter (first)
F. Noel B. Scatton (additional)

References 37 Referenced 68

{'key': 'e_1_2_2_2_1', 'first-page': '43P', 'article-title': 'Calcium permeability of the channels activated by N‐methyl‐D‐aspartate (NMDA) in mouse central neurones', 'volume': '377', 'author': 'Ascher P.', 'year': '1986', 'journal-title': 'J. Physiol.'} / J. Physiol. / Calcium permeability of the channels activated by N‐methyl‐D‐aspartate (NMDA) in mouse central neurones by Ascher P. (1986)
10.1016/0304-3940(83)90489-5
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{'key': 'e_1_2_2_12_1', 'first-page': '317', 'article-title': 'Excitatory amino acid‐induced changes in cyclic GMP levels in slices and cell suspension from the cerebellum', 'volume': '27', 'author': 'Garthwaite J.', 'year': '1981', 'journal-title': 'Adv. Biochem. Psychopharmacol.'} / Adv. Biochem. Psychopharmacol. / Excitatory amino acid‐induced changes in cyclic GMP levels in slices and cell suspension from the cerebellum by Garthwaite J. (1981)
10.1016/0306-4522(86)90164-8
{'key': 'e_1_2_2_14_1', 'first-page': '146', 'volume-title': 'Proceedings of the International Congress of Pharmacology, Vol. 5', 'author': 'Goldberg N. D.', 'year': '1973'} / Proceedings of the International Congress of Pharmacology, Vol. 5 by Goldberg N. D. (1973)
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{'key': 'e_1_2_2_24_1', 'first-page': '579', 'article-title': 'The effects of some organic “calcium antagonists” on calcium influx in presynaptic nerve terminals', 'volume': '16', 'author': 'Nachsen D. A.', 'year': '1979', 'journal-title': 'Mol. Pharmacol.'} / Mol. Pharmacol. / The effects of some organic “calcium antagonists” on calcium influx in presynaptic nerve terminals by Nachsen D. A. (1979)
{'key': 'e_1_2_2_25_1', 'first-page': '4207', 'article-title': 'Studies on guanylate cyclase. A new assay method for guanylate cyclase and properties of the cyclase from rat brain', 'volume': '249', 'author': 'Nakazawa K.', 'year': '1974', 'journal-title': 'J. Biol Chem.'} / J. Biol Chem. / Studies on guanylate cyclase. A new assay method for guanylate cyclase and properties of the cyclase from rat brain by Nakazawa K. (1974)
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{'key': 'e_1_2_2_35_1', 'first-page': '139', 'volume-title': 'Calcium Entry Blockers and Tissue Protection', 'author': 'Siesjo B. K.', 'year': '1985'} / Calcium Entry Blockers and Tissue Protection by Siesjo B. K. (1985)
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10.1042/bst0130916 / Biochem. Soc. Trans. / Sites of action of Ca2+ channel blockers in rat cortical synaptosomes by White E. J. (1985)

Dates

Type	When
Created	18 years, 11 months ago (Oct. 5, 2006, 4:20 p.m.)
Deposited	1 year, 11 months ago (Sept. 27, 2023, 5:32 a.m.)
Indexed	2 months, 2 weeks ago (June 21, 2025, 2:02 a.m.)
Issued	38 years, 2 months ago (July 1, 1987)
Published	38 years, 2 months ago (July 1, 1987)
Published Online	18 years, 11 months ago (Oct. 5, 2006)
Published Print	38 years, 2 months ago (July 1, 1987)

Funders 0

None

BibTeX

@article{Carter_1987, title={Ionic Mechanisms Implicated in the Stimulation of Cerebellar Cyclic GMP Levels by N‐Methyl‐D‐Aspartate}, volume={49}, ISSN={1471-4159}, url={http://dx.doi.org/10.1111/j.1471-4159.1987.tb03414.x}, DOI={10.1111/j.1471-4159.1987.tb03414.x}, number={1}, journal={Journal of Neurochemistry}, publisher={Wiley}, author={Carter, C. J. and Scatton, F. Noel B.}, year={1987}, month=jul, pages={195–200} }

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