Introductory Chapter: Biogenic Amines in Neurotransmission and Human Disease from the Endocrinologist’s Perspective

Abstract

There are about 1011 neurons and 1014 synaptic connections in the human brain. The neural circuitry is continuously sculpted in response to experience, modified as we learn and store memories, and irreversibly altered by the gradual loss of neurons and connections as we age [1]. Neuronal signals are transmitted from cell to cell at synapses. When an action potential arrives at the presynaptic site, the depolarization of the membrane opens voltage-gated calcium channels that are clustered in the presynaptic membrane. Calcium influx triggers the release of neurotransmitters which are stored in membrane-enclosed synaptic vesicles and released by exocytosis. The neurotransmitter provokes an electrical change in the postsynaptic cell by binding to and opening transmitter-gated ion channels. After the neurotransmitter is secreted into the synaptic cleft, it is rapidly removed: it is either destroyed by specific enzymes in the synaptic cleft or taken up by the presynaptic nerve terminal or by surrounding glial cells. Reuptake is mediated by a variety of Na+-dependent neurotransmitter symporters. The cycling of neurotransmitters allows cells to keep up with the high rates of release [1–3]. The chemical or electrical synapses can be excitatory or inhibitory. Excitatory neurotransmitters open cation channels, causing an influx of Na+ and also Ca+ in many cases, which reduces the threshold to fire an action potential. Inhibitory neurotransmitters open Cl or K+ channels, thereby making it difficult to depolarize the cell membrane. Depending on the secretion milieu, the type of the receptors they bind to, and the ionic conditions that they encounter, transmitters may be either inhibitory or excitatory. For example, acetylcholine may have inhibitory or excitatory effects depending on the type of the receptor it binds to. Usually glutamate and serotonin are excitatory, whereas γ-aminobutyric acid and glycine are inhibitory [1–4]. All neurotransmitter receptors fall into one of these classes based on their signaling mechanisms: