Epoxygenase metabolites of arachidonic acid inhibit vasopressin response in toad bladder

Journal Article · Tue Sep 01 00:00:00 EDT 1987 · American Journal of Physiology; (USA)

OSTI ID:5052921

Schlondorff, D; Petty, E; Oates, J A; Jacoby, M; Levine, S D ^[1]

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1. Albert Einstein College of Medicine, Bronx, NY (USA) Vanderbilt Univ., Nashville, TN (USA)

In addition to cyclooxygenase and lipoxygenase pathways, the kidney can also metabolize arachidonic acid by a NADPH-dependent cytochrome P-450 enzyme to epoxyeicosatrienoic acids (EETs); furthermore, 5,6-EET has been shown to alter electrolyte transport across isolated renal tubules. The authors examined the effects of three ({sup 14}C-labeled)-EETs (5,6-, 11,12-, and 14,15-EET) on osmotic water flow across toad urinary bladder. All three EETs reversibly inhibited vasopressin-stimulated osmotic water flow with 5,6- and 11,12-EET being the most potent. The effects appeared to be independent of prostaglandins EETs inhibited the water flow response to forskolin but not the response to adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) or 8-BrcAMP, consistent with an effect on cAMP generation. To determine whether these effects were due to the EETs or to products of their metabolism, they examined the effects of their vicinal diol hydrolysis products, the dihydroxyeicosatrienoic acids. Nonenzymatic conversion of labeled 5,6-EET to its vicinal diol occurred rapidly in the buffer, whereas 11,12-EET was hydrolyzed in a saturable manner only when incubated in the presence of bladder tissue. The dihydroxyeicosatrienoic acids formed inhibited water flow in a manner paralleling that of the EETs. The data support the hypothesis that EETs and their physiologically active dihydroxyeicosatrienoic acid metabolites inhibit vasopressin-stimulated water flow predominantly via inhibition of adenylate cyclase.

• OSTI ID: 5052921
• Journal Information: American Journal of Physiology; (USA), Vol. 253:3; ISSN 0002-9513
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
EPOXIDES
BIOLOGICAL EFFECTS
OXIDOREDUCTASES
ENZYME ACTIVITY
VASOPRESSIN
INHIBITION
AMP
ARACHIDONIC ACID
BLADDER
CARBON 14 COMPOUNDS
KIDNEYS
METABOLITES
PROSTAGLANDINS
TOADS
AMPHIBIANS
ANIMALS
AQUATIC ORGANISMS
BODY
CARBOXYLIC ACIDS
ENZYMES
HORMONES
LABELLED COMPOUNDS
MONOCARBOXYLIC ACIDS
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PEPTIDE HORMONES
PITUITARY HORMONES
URINARY TRACT
VERTEBRATES
550201* - Biochemistry- Tracer Techniques