Based on their structural and functional characteristics, the neurotransmitter receptor can be classified into two broad categories: metabotropic and ionotropic receptors. Ionotropic receptors form an ion channel pore. In contrast, metabotropic receptors are indirectly linked with ion channels on the plasma membrane of the cell through signal transduction mechanisms, often G proteins. Hence, G protein-coupled receptors are inherently metabotropic. Other examples of metabotropic receptors include tyrosine kinases and guanylyl cyclase receptors.
Both receptor types are activated by specific neurotransmitters. When an ionotropic receptor is activated, it opens a channel that allows ions such as Na+, K+, or Cl− to flow. In contrast, when a metabotropic receptor is activated, a series of intracellular events are triggered that can also result in ion channels opening or other intracellular events, but involve a range of second messenger chemicals.
This class of receptors includes the metabotropic glutamate receptors, muscarinic acetylcholine receptors, GABAB receptors, and most serotonin receptors, as well as receptors for norepinephrine, epinephrine, histamine, dopamine, neuropeptides and endocannabinoids.
The G protein-coupled receptors have seven hydrophobic transmembrane domains. Most of them are monomeric proteins, although GABAB receptors require heterodimerization to function properly. The protein's N terminus is located on the extracellular side of the membrane and its C terminus is on the intracellular side.
The 7 transmembrane spanning domains, with an external amino terminus, are often claimed as being alpha helix shaped, and the polypeptide chain is said to be composed of ~ 450-550 amino acids.