Accumulation of Radiolabeled N-Oleoyl-Dopamine in the Rat Carotid Body

Abstract

Exogenously administered dopamine (DA) is liable to penetrate into the carotid body, which, as opposed to the brain, has no endothelial barrier. DA is stored in the secretory vesicles of chemoreceptor cells. The vesicles are reminiscent of micelle-like entities and the hydrophilic properties of DA molecules make it dubious that DA could be packed and stay sustained in such an environment. The possible problems with the intravesicular arrangement of DA molecules may be one reason for thecomplex, often erratic, and as yet not full well understood DA action in the chemosensing process. DA displays a spate of varying effects, from stimulation to inhibition, on carotid chemosensory discharge and ventilation, depending on the species, the dose, and the presynaptic or postsynaptic dopamine D2 receptor it interacts with (see for review Gonzales et al., 1994). The present study was focused on extending the understanding of how the physicochemical properties of DA molecules could influence DA absorption by the carotid body. We investigated the hypothesis of whether administration of a substance in which the DA molecule is attached to a fatty acid chain motif could enhance carotid body uptake of DA. We chose N-oleoyl-dopamine (N-OL-DA) for the study, a product of bonding of the oleic acid chain to DA at its amino terminal, belonging to a class of novel biologically active lipid compounds, known under the summary name of dopamides (Pokorski and Matysiak, 1998). Recently, N-OL-DA has been identified as an endogenous participant of mammalian brain biochemistry with potent affinity to the central vanilloid VR1 receptor (Chu et al., 2003). N-OL-DA also is an active regulator of intracellular Ca (Chu et, 2003) and injected intracarotidly causes a transient inhibition of respiratory drive in the cat (unpublished observation), which recalls the respiratory effects of exogenous DA (Ide et al., 1995). This study seeks to