Association between inhibition of arachidonic acid release and prevention of calcium loading during ATP depletion in cultured rat cardiac myocytes

Journal Article · Fri Sep 01 04:00:00 EDT 1989 · American Journal of Pathology; (USA)

OSTI ID:5412451

Jones, R L; Miller, J C; Hagler, H K; Chien, K R; Willerson, J T; Buja, L M ^[1]

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1. Univ. of Texas, Dallas (USA)

The development of irreversible myocardial ischemic injury is associated with progressive degradation of membrane phospholipids, accumulation of arachidonate and other free fatty acids, and electrolyte derangements, including calcium accumulation. To study the relationship between arachidonate release and calcium loading during adenosine triphosphate (ATP) depletion in cardiac myocytes, the effects of two purported phospholipase inhibitors, mepacrine and U26,384, were evaluated. Cultured neonatal rat ventricular myocytes were pretreated for 90 minutes with 5 to 10 microM U26,384 (a steroidal diamine) or 10 to 50 microM mepacrine (an alkyl acridine) and then treated for 3 hours with 30 microM of the metabolic inhibitor, iodoacetic acid (IAA), with or without an additional dose of drug. IAA treatment resulted in a marked reduction in ATP level and a several-fold increase in free fatty acid radioactivity released from myocytes prelabeled with tritiated arachidonic acid (3H-AA). U26,384 produced substantial inhibition of the increased 3H-AA release, and was effective when given as a single pretreatment dose before IAA exposure or as continuous treatment before and during IAA exposure (for example, with 5 microM U26,384, the percentage of 3H-AA release versus IAA alone was 8% +/- 2% (SEM) (N = 15) for pretreatment only and 13% +/- 4% (N = 10) for continuous treatment). Mepacrine also resulted in significant reduction in 3H-AA release, but was more effective when given as continuous treatment (for example, with 50 microM mepacrine, the percentage of 3H-AA release versus IAA alone was 43% +/- 9% (N = 6) for pretreatment only and 22% +/- 7% (N = 9) for continuous treatment). More detailed analysis showed that U26,384 and mepacrine blocked the IAA-induced redistribution of 3H-AA into free fatty acids from other lipid species.

• OSTI ID: 5412451
• Journal Information: American Journal of Pathology; (USA), Journal Name: American Journal of Pathology; (USA) Vol. 135:3; ISSN AJPAA; ISSN 0002-9440
• Country of Publication: United States
• Language: English

Related Subjects

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550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METALS
ANIMALS
ARACHIDONIC ACID
ATP
BIOLOGICAL ACCUMULATION
BODY
CALCIUM
CARBOXYLIC ACIDS
CARDIOVASCULAR DISEASES
CARDIOVASCULAR SYSTEM
CELL CULTURES
DISEASES
ELEMENTS
ENZYME INHIBITORS
HEART
HYDROGEN COMPOUNDS
INHIBITION
ISCHEMIA
ISOTOPE APPLICATIONS
LIPASE
MAMMALS
METALS
MONOCARBOXYLIC ACIDS
NEONATES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
RATS
RODENTS
SECRETION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASCULAR DISEASES
VERTEBRATES