The Role of Histamine in Mental Illness and Its Attenuation With Vitamin C – Part II
The Role of Histamine in Mental Illness and its Attenuation with Vitamin C – Part II
Chapter 2: A Review of Related Literature and Research
Introduction:
“Histamine was synthesized in 1907 and later isolated from mammalian tissues” (Katzung, 1998, p. 261). It has multiple roles in the body, including neuromodulation and neurotransmission, allergic and inflammatory mediator, and gastric acid secretion stimulator. Common food sources of histamine are red wine and strawberries (Firshein, 1996). The organic chemical name for histamine is 2-(4-imidazoyl)ethylamine. It is formed from decarboxylation of the amino acid histidine, via the action of the enzyme histidine decarboxylase. The body’s usual mode of histamine detoxification is methylation by the amino acid methionine (Pfeiffer, 1987). Excessive amounts of histamine released into the bloodstream can dangerously raise pulse and lower blood pressure to the point of shock and sometimes death. The mechanism of this phenomenon is described below.
Mast cells contain granules filled with histamine, and this is where most tissue histamine resides. Histamine that is bound to mast cells (or functionally related cells called basophils) is inactive. Exposure to an antigen (allergen) causes the antigen-specific IgE antibody to connect with mast cells (the primary immune response). Reexposure to the same antigen results in antibody signaling to mast cells to release histamine (the secondary immune response) (Weinstein, 1987). Histamine’s actions include vascular permeability and bronchoconstriction (Abbas, Lichtman, & Pober, 2000), which can lead to both asthma and dangerous drops in blood pressure. Excess mast cells, known as mastocytosis, can cause a variety of behavioral disturbances, including “diminished attention and memory, and the affective changes of anger, irritability, and, to a lesser extent, depression” (Rogers, et. al., 1986, p. 437).
Brain histamine neurons originate in the tuberomammillary nucleus (TM), which is located within the hypothalamus. These neurons project throughout the nervous system, including the olfactory system and spinal cord (Wada, Inagaki, Itowi, & Yamatodani, 1991). Histaminergic neurons stimulate the cerebral cortex either directly or indirectly via activation of serotonergic neurons (Blandina et al., 2004). Some histaminergic neurons store neuroactive substances such as galanin, GABA, substance P, glutamate decarboxylase, and adenosine deaminase (Blandina et al., 2004). Brain histamine increases wakefulness, locomotor activity, sexual behavior, and release of adrenocorticotropic hormone (ACTH), and decreases slow-wave sleep, feeding, and growth hormone production (Wada, Inagaki, Yamatodani, & Watanabe, 1991).
In order to better understand histamine’s role in neurotransmission, an introduction/review of neurotransmitters, their receptors, and the signal transduction pathways downstream of the receptors will be presented. A neurotransmitter is a chemical which effects communication between two nerve cells called neurons. It is synthesized inside the neuron (histamine being an exception), travels to the end of the neuron (axon), is released into the extracellular space between two neurons (synapse), and then binds to a specific receptor on the ‘receiving’ neuron, usually the dendrite. After the neurotransmitter activates the receptor, it soon comes off the receptor and is taken up again by the original releasing axon, termed ‘reuptake’. The neurotransmitter’s action is specific and local, or paracrine. This is in contrast to hormones that are released in the other organs of the body, which generally disperse to all tissues, and affect all cells that have the hormone’s receptor (endocrine). However, some neurotransmitters are also hormones; as mentioned previously, histamine is one of them.
There are three classical types of neurotransmitters: peptides, which are small protein fragments, acetylcholine, and amino acids/amino acid derivatives. There are many different peptide neurotransmitters, and some of them interact with histamine, vitamin C, or both. Some examples of the above interactions will be described later. Acetylcholine acts very similar to an amino acid/amino acid derivative neurotransmitter, but is much more hydrophobic and is lipid (fat) related. Acetylcholine can be either inhibitory or excitatory to neurotransmission, depending on the receptor it binds to. Acetylcholine plays a major role in both memory and learning. Amino acids that can act as neurotransmitters are glycine, gamma-amino butyric acid (GABA), glutamate, and aspartate. Glycine and GABA are both neutrally-charged amino acids, and are inhibitory neurotransmitters; that is, they generally inhibit neurotransmission in the entire downstream neuron. Glutamate and aspartate are both acidic amino acid, and both are strong excitatory neurotransmitters, although they do have one inhibitory receptor, discussed below.
The amino acid