DOPAMINE-O-SULFATE IN THE DOG: MEASUREMENT, DISTRIBUTION AND CARDIOVASCULAR ACTIONS (CATECHOLAMINE, CEREBROSPINAL FLUID)
Abstract
Dopamine-O-sulfate (DAS) is found in the tissues of many mammals. However, little is known concerning its distribution or physiological activity. Major reasons for the limited information have been the lack of detection methods and authentic DAS. This document reports the results of three studies. The first study compared two methods for estimation of DAS. The first is an alumina adsorption assay which utilizes acid hydrolysis and measures free and conjugated dopamine (DA). The second is a newly developed method which measures the isomers of DAS in plasma and CSF. The levels of conjugated DA (102.6 pmol/ml) and DAS (26.6 pmol/ml) were found to differ in dog plasma. Other experiments investigated some of the reasons for this difference. The time courses of free DA release during acid hydrolysis of DAS and dopamine glucuronide were found to differ from that seen with dog plasma. The second study examined the effects of intravenous administration of a mixture of the DAS isomers on blood pressure (BP) of the anesthetized dog. The effects of administration of each of the DAS isomers on BP and renal and femoral arterial blood flow were then examined. The isomer mixture produced a dose-dependent decrease in BP. However, administration of authentic samples of either isomer separately or a mixture of authentic samples of both isomers produced no significant effect on BP or blood flow through the renal or femoral beds. Increasing volumes of cold vehicle were found to decrease BP and may account for the decreases seen with administration of the isomer mixture. The final study examined the ability of DAS to cross the blood-CSF barrier in the anesthetized dog. DAS was administered in a bolus of 78.4 nmol/kg, followed by infusion of 1.1 nmol/kg(.)min; this was designed to raise plasma levels to 200 pmol/ml. In three of the four test animals from whom complete plasma and CSF samples were obtained, increased CSF DAS levels were seen within 60 min after the initial bolus. Values of DAS in CSF and plasma varied in control animals, but these fluctuations did not account for the increases seen in the test animals, indicating that DAS can cross the blood-CSF barrier.
Degree
Ph.D.
Subject Area
Pharmacology
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