Neurotransmitters metabotropic

Cartmell, J. Schoepp, D. D. (2000). Regulation of neurotransmitter release by metabotropic glutamate receptors. J. Neurochem. 75, 889-907. 

Metabotropic receptor A G protein-coupled neurotransmitter receptor. 

V-methyl-D-aspartate receptors. Glutamate is the major excitatory neurotransmitter in the central nervous system (Ch. 15). Its receptors can be divided into three types AMPA/kainate, NMDA and metabotropic receptors. NMDA receptors are composed of two different types of subunit - NR1 and NR2. They play an important role in the induction of synaptic plasticity and excitotoxicity. 

A variety of substances have been found to serve as neurotransmitters in the nervous system. Most of these have actions outside the nervous system as well. Classically, the term neurotransmitter implies ionotropic actions on neurons, while those with metabotropic actions are regarded as neuromodulators. This distinction is blurred, however, by the fact that many substances can have either action, depending on the receptor to which it binds. Table 2.1 summarizes the major classes of neurotransmitters and their receptor-effector mechanisms. 

The excitatoiy amino acids (EAA), glutamate and aspartate, are the principal excitatory neurotransmitters in the brain. They are released by neurons in several distinct anatomical pathways, such as corticofugal projections, but their distribution is practically ubiquitous in the central nervous system. There are both metabotropic and ionotropic EAA receptors. The metabotropic receptors bind glutamate and are labeled mGluRl to mGluRB. They are coupled via G-proteins to phosphoinositide hydrolysis, phospholipase D, and cAMP production. Ionotropic EAA receptors have been divided into three subtypes /V-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA), and kainate receptors (Nakanishi 1992). 

A variety of peptides are utilized in the nervous system as neurotransmitters. Unlike other neurotransmitters, which can be synthesized in various parts of the neuron like the axon terminals, neuropeptides are produced by gene transcription and translation. They may colocalize and be coreleased with ACh, monoamines, or amino acid neurotransmitters. Their receptors are metabotropic and may work through a variety of effector mechanisms. Neuropeptides are formed and degraded by a variety of peptidase enzymes. 

Receptor-effector mechanisms include (1) enzymes with catalytic activities, (2) ion channels that gate the transmembrane flux of ions (ionotropic receptors), (3) G protein-coupled receptors that activate intracellular messengers (metabotropic receptors), and (4) cytosolic receptors that regulate gene transcription. Cytosolic receptors are a specific mechanism of many steroid and thyroid hormones. The ionotropic and metabotropic receptors are discussed in relevance to specific neurotransmitters in chapter 2. 

The postsynaptic receptors respond either rapidly (ionotropic t e) or slowly (metabotropic type) depending on the nature of the neurotransmitter. 

There are two major types of receptor which are activated by neurotransmitters. These are the ionotropic and metabotropic receptors. The former receptor type is illustrated by the amino acid neurotransmitter receptors for glutamate, gamma-aminobutyric acid (GABA) and glycine, and the acetylcholine receptors of the nicotinic type. These are examples of fast transmitters in that they rapidly open and close the ionic channels in... 

In contrast to the ionotropic receptors, the metabotropic receptors are monomeric in structure and unique in that they show no structural similarity to the other G-protein-coupled neurotransmitter receptors. They are located both pre- and postsynaptically and there is experimental evidence that they are involved in synpatic modulation and excitotoxicity, functions which are also shared with the NMDA receptors. To date, no drugs have been developed for therapeutic use which are based on the modulation of these receptors. 

Figure 6.4. Molecular structure of the metabotropic 5-HT4 receptor. This seven-membrane spanning structure is typical of most metabotropic neurotransmitter...

---