Dopaminergic Mechanisms in Gastrointestinal Motility
Dopamine is synthesized from tyrosine as part of the pathway for biosynthesis of catecholamines. Hydroxylation of tyrosine to dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase is the rate-limiting step in the biosynthetic pathway. The enzyme DOPA decarboxylase catalyzes the synthesis of dopamine from DOPA. Direct evidence supporting a role for dopamine as a neurotransmitter in the gastrointestinal tract is lacking. However, several approaches have been employed that provide indirect support that dopamine may act as a neurotransmitter in the gut. Support for dopamine-mediated modulation of gastrointestinal motor function is based substantially on studies employing agonists and antagonists that are relatively selective for dopamine receptors. Dopamine receptors belong to a large family of neurotransmitter receptors that are coupled to their specific cellular functions via guanine nucleotide regulatory G proteins. Central dopaminergic pathways may modulate the interdigestive migrating myoelectric complex (IMMC) of the gastrointestinal tract. In the fasted dog, intracerebroventricular administration of dopamine increased the duration of the interval between two consecutive IMMCs.