The Role of Histamine in Mental Illness and Its Attenuation With Vitamin C – Part II
derivative neurotransmitters are dopamine, norepinephrine, serotonin, and histamine. Both dopamine and norepinephrine are formed from a common pathway: phenylalanine -> tyrosine -> l-dopa -> dopamine -> norepinephrine -> epinephrine. The first two molecules, phenylalanine and tyrosine, are both bona fide amino acids, and the last four molecules are amino acid derivatives. Dopamine is an inhibitory neurotransmitter; it often achieves this by activating downstream pathways that ultimately become inhibitory. Two major roles that dopamine plays are regulation of the hypothalamus, and maintenance of fine motor control; Parkinson’s disease is the result of excessive loss of dopamine-receiving neurons. Excessive dopamine levels can result in psychosis, and all of the classic antipsychotic drugs inhibit dopamine neurotransmission. Dopamine is often known as the pleasure hormone, since drugs like heroin, cocaine, nicotine, and marijuana act to release dopamine into synapses.
Norepinephrine can be either excitatory or inhibitory, again depending on the receptor it binds to. It plays major roles in attention and arousal. Epinephrine does not play a significant neurotransmitter role in the brain. Serotonin, otherwise known as 5-hydroxytryptamine, is formed by the pathway tryptophan -> 5-hydroxytryptophan -> 5-hydroxytryptamine. As in the dopamine/norepinephrine pathway, the first molecule in the pathway, tryptophan, is a true amino acid. Serotonin is similar to norepinephrine in that it can be either excitatory or inhibitory. Serotonin appears to be involved in diverse biochemical and behavioral functions, including neuroendocrine control, sleep, appetite, and temperature regulation. Its complex relationship with neuroendocrine systems has led many experts to call serotonin the ‘key neurotransmitter,’ or the ‘master hormone.’ However, as discussed in detail below, histamine may equal or exceed serotonin in neuroendocrine influence.
As mentioned previously, histamine is formed directly from the amino acid histidine. Histamine is unique among the amino-acid derived neurotransmitters in that it is not released from an axon, and is not taken up by the releasing axon after its neurotransmission is completed. It is always excitatory, and ironically that excitation may eventually lead to major depression, as will be discussed later. Histamine shares many physiological roles with serotonin, including all four of the roles mentioned above (neuroendocrine control, sleep, appetite, and temperature regulation). Interestingly, serotonin is often released along with histamine during allergic reactions. Like norepinephrine, histamine plays a role in arousal, and like acetylcholine, it also plays a role in learning and memory. Histamine also is implicated in psychosis just as dopamine is, although it is low histamine levels that usually are the culprit, whereas high dopamine levels appear to cause psychosis. Since histamine is always excitatory, it is functionally related to the amino acid neurotransmitters glutamate and aspartate. In short, histamine plays diverse biochemical roles that are shared by almost all other neurotransmitters, and in turn influences many roles of the other neurotransmitters.
Neurotransmitter receptors are located on the receiving end of the neurotransmitter signal (usually the dendrite cell), and are embedded in the outside fatty layer of the cell, termed the plasma membrane. Often there are multiple types of receptors for each neurotransmitter. There are two types of GABA receptors, termed GABAA and GABAB; both are inhibitory. There is only one glycine receptor, and as mentioned earlier it is inhibitory. There are at least four main receptors for both glutamate and aspartate; interestingly the two amino acids share all four receptors, three of which are termed ionotropic and one metabotropic. The ionotropic receptors are called N-Methyl-D-aspartate (NMDA), AMPA, and Kianate. The three ionotropic receptors are all excitatory. The metabotropic receptor group has three subgroups; two are inhibitory and one is excitatory.
There are three types of acetylcholine receptors. Two of them are termed cholinergic muscarinic receptors, and are given the abbreviations M1 and M2. M1 receptors are excitatory, and M2 receptors are inhibitory. The third type of acetylcholine receptor is called the cholinergic nicotinic receptor, and is excitatory. There are two dopamine neurotransmitter receptors, termed D1 and D2; both are inhibitory. The neurotransmitter receptors for norepinephrine are the most complicated of all, besides possibly the glutamate/aspartate receptors. The two major types of norepinephrine receptors in the brain, alpha (a) and beta (b). These are both further divided into a1 and a2 receptors, and b1 and b2 receptors. The a1 and b1 receptors are both excitatory, and the a2 and b2 receptors are both inhibitory.
There are four main types of