Selective accumulation of biotin in arterial chemoreceptors: requirement for carotid body exocytotic dopamine secretion

Abstract

Biotin is a water-soluble vitamin required for the function of carboxylases as well asfor the regulation of gene expression. Here, we report that biotin accumulates in unusually largeamounts in cells of arterial chemoreceptors, carotid body (CB) and adrenal medulla (AM). Weshow in a biotin-deficient rat model that the vitamin rapidly disappears from the blood andother tissues (including the AM), while remaining at relatively high levels in the CB. We havealso observed that, in comparison with other peripheral neural tissues, CB cells contain highlevels of SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin.Biotin-deficient rats show a syndrome characterized by marked weight loss, metabolic lacticacidosis, aciduria and accelerated breathing with normal responsiveness to hypoxia. Remarkably,CB cells from biotin-deficient animals have normal electrophysiological and neurochemical (ATPlevels and catecholamine synthesis) properties; however, they exhibit a marked decrease in the sizeof quantal catecholaminergic secretory events, which is not seen in AM cells. A similar differentialsecretory dysfunction is observed in CB cells treated with tetrabenazine, a selective inhibitor ofthe vesicular monoamine transporter 2 (VMAT2). VMAT2 is highly expressed in glomus cells (incomparison with VMAT1), and in biotin-deficient animals VMAT2 protein expression decreases in parallel with the decrease of biotin accumulated in CB cells. These data suggest that biotinhas an essential role in the homeostasis of dopaminergic transmission modulating the transportand/or storage of transmitters within small secretory granules in glomus cells.