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Research ArticleArticle

On the Action of Δ9-Tetrahydrocannabinol as an Inhibitor of Sodium- and Potassium-Dependent Adenosine Triphosphatase

EFRAÍN TORO-GOYCO, M. B. RODRÍGUEZ and A. M. PRESTON
Molecular Pharmacology January 1978, 14 (1) 130-137;
EFRAÍN TORO-GOYCO
Department of Biochemistry and Nutrition, University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936
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M. B. RODRÍGUEZ
Department of Biochemistry and Nutrition, University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936
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A. M. PRESTON
Department of Biochemistry and Nutrition, University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936
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Abstract

Chromatographically pure Δ9-tetrahydrocannabinol (Δ9-THC) was tested in vitro for inhibitory activity on sodium- and potassium-stimulated ATPase (ATP phosphohydrolase, EC 3.6.1.3) from various sources. Concentrations of 3 µM Δ9-THC inhibited by 50% enzyme preparations with specific activities of 1200-1500 nmoles of Pi per minute per milligram of protein. Rat brain ATPases were much more sensitive to Δ9-THC than to equal concentrations of ouabain. The kinetics of inhibition of electric eel ATPases seemed to be noncompetitive with respect to ATP. Rat brain ouabain-insensitive ATPases were also inhibited by Δ9-THC, and preliminary kinetic data indicated that inhibition is competitive with respect to ATP. In Ehrlich ascites tumor cells (107 cells/ flask), 60 µM Δ9-THC inhibited nucleoside ([3H]thymidine) incorporation without exerting any significant effect on the viability of cells as measured by O2 consumption. Particulate ATPases isolated from cells exposed to Δ9-THC were found to have significantly lower specific activity than cells in control media, 123 ± 36 compared with 172 ± 16 nmoles of Pi per minute per milligram of protein (p < 0.005, n = 16). The hypothesis is advanced that several of the observed physiological effects of Δ9-THC can be explained on the basis of its ATPase-inhibitory activity.

ACKNOWLEDGMENTS We thank Professor L. S. Harris, Department of Pharmacology, Medical College of Virginia, for his generous gift of Δ9-THC, and Professor J. del Castillo, Neurobiology Institute, this institution, for the electric eels. We thank Drs. J. M. Cimadevilla and H. Jering for their criticisms and suggestions, and Mr. Juan Caloca for the illustrations.

  • Copyright © 1978 by Academic Press, Inc.

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Molecular Pharmacology
Vol. 14, Issue 1
1 Jan 1978
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Research ArticleArticle

On the Action of Δ9-Tetrahydrocannabinol as an Inhibitor of Sodium- and Potassium-Dependent Adenosine Triphosphatase

EFRAÍN TORO-GOYCO, M. B. RODRÍGUEZ and A. M. PRESTON
Molecular Pharmacology January 1, 1978, 14 (1) 130-137;

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Research ArticleArticle

On the Action of Δ9-Tetrahydrocannabinol as an Inhibitor of Sodium- and Potassium-Dependent Adenosine Triphosphatase

EFRAÍN TORO-GOYCO, M. B. RODRÍGUEZ and A. M. PRESTON
Molecular Pharmacology January 1, 1978, 14 (1) 130-137;
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