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Exogenous gamma-linolenic acid alters hormone stimulated cyclic AMP levels in U937 cells
R C Cantrill1, P P Patterson, G W Ells
1EFAMOL Research Institute, Kentville, Nova Scotia, Canada.
Abstract:
Polyunsaturated fatty acids are selectively cytotoxic in culture. Incorporation of these fatty acids leads to profound changes in membrane fatty acid composition which in turn may alter the activity of transmembrane receptor/effector systems. In U937 cells, hormone stimulated production of cyclic AMP can be reduced by 30% following incubation with gamma-linolenic acid (18:3n-6). It is suggested that beta-adrenoreceptor number, subtype and adenylyl cyclase stimulation may be regulated by alterations in membrane fatty acid composition as a result of changes in the levels of polyunsaturated fatty acids and alterations in eicosanoid production.
Insights
Polyunsaturated fatty acids show selective cytotoxicity. Gamma-linolenic acid alters cell membranes, reducing hormone-stimulated cyclic AMP production in U937 cells, suggesting membrane fatty acid changes regulate receptor activity.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Polyunsaturated fatty acids (PUFAs) exhibit selective cytotoxicity in cellular models.
- Changes in cell membrane fatty acid composition can impact transmembrane receptor signaling.
- Eicosanoid production is linked to PUFA metabolism and cellular function.
Purpose of the Study:
- To investigate the effect of polyunsaturated fatty acids on cellular signaling pathways.
- To determine if gamma-linolenic acid influences hormone-stimulated cyclic AMP production.
- To explore the regulatory role of membrane fatty acid composition in receptor/effector system activity.
Main Methods:
- Incubation of U937 cells with gamma-linolenic acid (18:3n-6).
- Measurement of hormone-stimulated cyclic AMP production.
- Analysis of changes in membrane fatty acid composition.
Main Results:
- Polyunsaturated fatty acid incorporation significantly altered membrane fatty acid profiles.
- Gamma-linolenic acid incubation reduced hormone-stimulated cyclic AMP production by 30% in U937 cells.
- These findings suggest a link between membrane lipid composition and signal transduction.
Conclusions:
- Alterations in membrane fatty acid composition, particularly PUFAs, can modulate transmembrane receptor/effector system activity.
- Changes in gamma-linolenic acid levels may influence beta-adrenoreceptor function and adenylyl cyclase activity.
- PUFA-induced changes in membrane composition are implicated in regulating cellular responses and eicosanoid production.