| Figure 1. |
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| Schematic model of a prototypic dopaminergic nerve terminal illustrating the life cycle of dopamine and depicting mechanisms which modulate dopamine release and synthesis. Invasion of the terminal by a nerve impulse results in the Ca2+-dependent release of dopamine. This release process is attenuated by release of modulating autoreceptors. Increased impulse flow also stimulates tyrosine hydroxylation. This appears to involve the phosphorylation of tyrosine hydroxylase (TH), resulting in the conversion to an activated form with greater affinity for tetrahydrobiopterin cofactor. The rate of tyrosine hydroxylation can be attenuated by (a) activation of synthesis-modulating autoreceptors, which may function by reversing the kinetic activation of TH, and (b) end-product inhibition by intraneuronal dopamine which competes with cofactor for a binding site on TH. Release- and synthesis-modulating autoreceptors may represent distinct sites. Alternatively, one site may regulate both functions through distinct transduction mechanisms. The dopamine transporter is a unique component of the dopamine terminal, which serves an important physiological role in the inactivation and recycling of dopamine release into the synaptic cleft. |
published 2000