Molecular Biology of Chemoreceptor Function: Induction of Tyrosine Hydroxylase in the Rat Carotid Body Elicited by Hypoxia

Abstract

Dopamine is the most abundant catecholamine stored in glomus cells of the rat carotid body (9, 13, 19). Recent evidence (10) suggests that dopamine participates in the early response to hypoxia; however, the molecular mechanism whereby dopamine is released and participates in the chemoreceptor function has not yet been elucidated. In order to improve our present understanding of these mechanisms, the changes in the activity and properties of tyrosine hydroxylase — the rate-limiting enzyme in the synthesis of dopamine — have been monitored at various times after exposure to hypoxic conditions. It is generally accepted that in nervous tissue the activity of tyrosine hydroxylase increases when the rate of firing of catecholaminergic neurons is increased. The duration of the enhanced neuronal activity and the cellular localization of tyrosine hydroxylase determine whether the affinity of tyrosine hydroxylase for its cofactor (20)or the synthesis rate of tyrosine hydroxylase is increased (2). When the increase in activity is long-lasting, tyrosine hydroxylase synthesis is increased. Since theT _1/2 of tyrosine hydroxylase is greater than 20 h, a long-term increase of tyrosine hydroxylase activity ensues.