Vasoactive amines

Patients receiving monoamine oxidase inhibitors (MAOI) as antidepressant therapy have been especially subject to the hypertensive effects of vasoactive amines (52). These dietary amines have also been impHcated as causative agents ia migraine. Other aaturaHy occurring alkaloids (qv) have been recognized for centuries as possessing neurological stimulant and depressant properties. 

Ubiquitous mitochondrial monoamine oxidase [monoamine oxygen oxidoreductase (deaminating) (flavin-containing) EC 1.4.3.4 MAO] exists in two forms, namely type A and type B [ monoamine oxidase (MAO) A and B]. They are responsible for oxidative deamination of primary, secondary, and tertiary amines, including neurotransmitters, adrenaline, noradrenaline, dopamine (DA), and serotonin and vasoactive amines, such as tyramine and phenylethylamine. Their nonselec-tive and selective inhibitors ( selective MAO-A and -B inhibitors) are employed for the treatment of depressive illness and Parkinson s disease (PD). 

Inflammation is a non-specific reaction which can be induced by a variety of agents apart fiom microorganisms. Lymphokines and derivatives of arachidonic acid, including prostaglandins, leukotrienes and thromboxanes are probable mediators of the inflammatory response. The release of vasoactive amines such as histamine and serotonin (5-hydroxytryptamine) firm activated or damaged cells also contribute to inflammation. 

Upon activation, mast cells release numerous mediators, including vasoactive amines, proteases, pro-inflammatory cytokines (e.g. IL-ip, IL-6, IL-18 and TNF-a) and also regulatory Th2 cytokines (e.g. IL-4, IL-10 and IL-13) (Burd et al., 1989 Gordon and Galli, 1990 Marietta el al., 1996 Toru et al., 1998 Aoki et al., 1999 Lorentz et al, 2000). Therefore, the mastocytosis in the infected mucosa represents an immunopathological rather than a protective response. Indeed, our studies have shown that expulsion of T. spiralis from TNF-Rl / or iNOS / mice was achieved in the absence of a substantial mastocytosis and subsequent amelioration of enteropathy (Lawrence etal., 1998, 2000). 

Invasion of the tissues by an infective agent initiates an inflammatory response in the animal. This is non-specific and is mediated primarily by substances released from tissues that are damaged as a result of either trauma or the toxic effects of the infective agent. The major mediator is the vasoactive amine histamine, which causes an increased local blood flow and capillary permeability, resulting in local oedema. A major aspect of the inflammatory response is the involvement of large numbers of phagocytic cells, particularly the polymorphonuclear leucocytes. These are chemotactically attracted to the inflamed tissues and are mainly responsible for the elimination of particulate material. This often results in the destruction of many of these cells and the formation of pus. 

IgE is known as a cytophilic immunoglobulin because of its ability to bind to cells, which may account for its low concentration in body fluids. When IgE reacts with an antigen it causes degranulation of the mast cell to which it is bound, with the release of vasoactive amines such as histamine. This process may well be helpful in initiating the inflammatory response but in allergic individuals the reaction is excessive and leads to a hypersensitive or over-reactive state. 

A direct effect of vasoactive amines on the organism which are not degraded in GI tracts due to the lack of mono- and diaminooxidase (MAO and DAO) or their blockade by medicines or alcohol. This group of amines includes tyramine (in Cheddar, emmental, roquefort cheeses, pickled fish, and walnuts), phenylethylamine (in chocolate), serotonin (in bananas), octopamine (in lemons), and histamine (in fermented foods, e.g., blue cheeses, but also in strawberries, tomatoes, wines, and in mackerel that have not been stored properly [scombrotoxin illness]). 

That amines formed from naturally occurring amino acids are partly responsible for chronic hypertension is a rather attractive hypothesis first suggested by the experiments of Holtz (35). Besides the normal metabolic enzymes of amino acids, tissues, especially kidney, liver, and brain, contain amino acid decarboxylases, some of them specific for certain amino acids, some less so. These are anaerobic enzymes. After decarboxylation, certain monoamines are deaminated by amine oxidases which are sensitive to oxygen tension. The best known of these oxidases is the enzyme of Blaschko, Richter, and Schlossmann (9), which may be a mixture of three or more (29), and which is specific for many nonsubstituted vasoactive amines found in the body, with the notable exception of histamine. 

Recently, a new and potentially safer technique of disruption of the BBB, called a biochemical disruption, has been developed. In contrast to osmotic disruption, this method is based on the observation that some substances can selectively open only brain tumor capillaries leaving normal brain capillaries unaffected. The substances used for this procedure are vasoactive leukotrienes, such as leukotriene C4 [113], vasoactive amines such as bradyki-nin, histamine, and the synthetic bradykinin analog RMP-7, Cereport [114], or insulin [115], The mechanism of leukotriene C4 effect was shown to be related to the abundance of g-glutamyl transpeptidase (g-GTP) in normal capillaries and its decreased amount in tumors. 

Biogenic amines are often mentioned but they are not the only mechanism. The indirect systemic effect of vasoactive amines not degraded in the gastrointestinal tract occurs if the release of enzymes by enterocytes—mono and diaminooxidase (MAO and DAO, respectively)—is lacking or if it is blocked by medicines or alcohol (Tuormaa, 1994). 

Mast cell)/ vasoactive amines, chemical mediators... 

H20. Henson, P. M., and Cochrane, C, G., Acute immune complex disease in rabbits. The role of complement and of a leucocyte-dependent release of vasoactive amines from platelets. /. Exp. Med. 133, 554-571 (1971). 

Primary mediators Vasoactive amines, eicosanoids IFN-y and other cytokines, growth factors, reactive oxygen species, hydrolytic enzymes... 

Histamine, vasoactive amine from mast cells, basophils and platelets... 

COCAINE MAOIs Hypertensive crisis Due to i metabolism of vasoactive amines Avoid concurrent use... 

With each blink the antigen-coated contact lens mechanically traumatizes the tarsal conjunctiva. This process causes the release of mediators, such as neutrophil chemotactic factor and eosinophil chemotactic factor, which attract inflammatory cells (e.g., neutrophils, eosinophils, mast cells, and basophils). The immunologic sequence of events results in an increase in tear immunoglobulins IgE and IgG and C3 anaphylatoxin. The tear immunoglobulins and C3 anaphylatoxin then interact with the inflammatory cells produced from the mechanical trauma. This interaction causes the release of vasoactive amines, resulting in subsequent clinical manifestations. Papillae formation is related to structural changes in the conjunctival epithelium and stroma associated with increased eosinophils and inflammatory cells. 

Haslam RJ, Vanderwel M. Inhibition of platelete adenylate cyclase by l-0-alkyl-2-0-acetyl-sn-glyceryl-3-fdiosphoryldioline (platdet-activating factor). J Biol Chon 1982 257 6879-6885 Henson PM. Release of vasoactive amine from rabbit platelets induced by sensitized mmoniidear leukocytes and antigens. J Exp Med 1970 131 287-304... 

Doukas, J., Shepro, D. and Hechtman, H.B. (1987). Vasoactive amines directly modify endothelial cells to affect polymorphonuclear leukocyte diapedesis in vitro. Blood 69, 1563-1569. 

Inhibition of liver MAO leaves the patient vulnerable to the so-called wine-and-cheese syndrome, with adverse cardiovascular effects caused by absorption of such vasoactive amines as tyramine into the general circulation [for review, see Blackwell et al. (23)], The syndrome can include severe headache and hypertension and may lead to cerebral hemorrhage and death. Although this is a real risk, it seems likely that fears of MAOfood interactions may have been grossly exaggerated. Pare (24) reviewed the evidence in 1985 and noted that despite the widespread use of MAO inhibitors in the previous decade there had only been 17 reports of food interactions with phenelzine (19) and none of these proved fatal. With tranylcypromine (23) seven deaths had been reported, but in only two of these could a definite relationship with diet be established. 

The PMN cells include neutrophils, eosinophils, and basophils. Neutrophils make up 60-75% of circulating WBCs and provide the first line of defense against microbes that penetrate the normal barriers of skin. They are extremely efficient phagocytes and are a source of inflammatory cytokines and lipid mediators such as PGs, LTs, and platelet-activating factor. Eosinophils are involved in allergy and provide protection against parasites. Basophils contain vasoactive amines such as histamine, serotonin, and heparin, as well as precursors for PGs and LTs. Release of these pharmacological materials by the basophils is responsible for the anaphylactic reaction. These factors also serve as chemoattractants for neutrophils and eosinophils to sites of inflammation. 

It causes the secretion of vasoactive amines from platelets by a calcium-... 

The vasoactive amines phentolamine and papaverine are occasionally used as intracavernosal therapy, usually in combination with alprostadil, although their use for erectile dysfunction is off-label. Moxisylyte is another vasoactive agent used as intracavernosal therapy. The drug is approved in several European countries, but is not approved in the United States. The advantages over alprostadil are that with moxisylyte, sexual stimulation is still required to achieve full erection and that detumescence occurs on ejaculation. 

In 1982, a new era for erectile dysfunction started when Virag (156) showed that penile injection of a vasoactive amine—papaverine (9)—could result in erection without sexual... 

Fig. 6. Diagram to show how, when allergen becomes bound to mast-cell fixed reaginic antibody (IgE), the vasoactive amines mediating immediate hypersensitivity are discharged. The mast cell is capable of becoming recharged, etc. Excess IgG-antibodies can block the access of allergen, which acts only when bound to two IgE molecules.

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