here's one more article that explains the relation of histamines to adrenals, http://lymedisease.medical-topics.com/tag/histamine/
i've cut and pasted the "highlights" below...see you all in a few months:)

Literature Review:


There is a considerable amount of evidence supporting the theory that histamine is directly involved in the stress response induced biochemical changes. In non-stressed rats, histamine interacts normally with a & b-adrenergic and muscarinic cholinergic receptor. He stressed rats, histamine interacts only with a-adrenergic, non-b-adrenergic receptors (Bugajski, 1984). Many of the anti-anxiety drugs work by increasing the activity of the major inhibitory neurotransmitter GABA, or GABA receptor activation. Interestingly, GABA inhibits the release of histamine (Jacobs, Yamatodani and Timmerman, 2000). Administration of histidine, the amino acid precursor of histamine-induced strange 'behavior mock fight' in rats, and established that both muscarinic cholinergic receptors, H1 and extend this behavior (Pilch, Rogoz and Skuza, 1982).

Stress can trigger release of histamine, which in turn acts to release the stress hormones ACTH, CRH, prolactin (PRL) and vasopressin (Brown, Stevens, & Haas, 2001). At rest and during stress, CRF, noradrenaline and glucocorticoids such as cortisol and maintain CNS homeostasis of the immune system. Alter the homeostasis of this excess histamine by changing the immune system to a pro-inflammatory status (Chrousos, 2000). Press CRF is normally initiated by the neurotransmitters dopamine, serotonin and norepinephrine (Tuomisto & Mannisto, 1985). Elevated levels of histamine can act to "kidnap" the required distance from the release of neurotransmitters CRF mentioned above, in order to unbalance the HPA axis and, finally, the central nervous system homeostasis. In fact, it has been shown that histamine is a potent stimulator of the organs of the pituitary and adrenal (Bugajski & Gadek, 1983). There is also evidence that histamine plays an important role in physiological responses to chronic stress, keep your brain in a Warning state (Parmentier, et al., 2002) against a real or imaginary challenge.

There are two types of immune responses: Th1 and Th2. Th1 immune response is one that is directed against the microbes. Th2 immune response is one that is directed against otherwise harmless protein called antigens. Excess cortisol shifts the immune response toward Th2 (Hurwitz & Morgenstern, 2001). This can initiate a vicious circle of positive feedback, since allergic reactions can promote and maintain the HPA axis in business, eventually leading to Depression (Hurwitz & Morgenstern, 2001). Hyperactivity of the HPA axis, in turn, leads to overproduction of cortisol. The success of feedback is supported by the finding that stress increases cortisol levels and high levels of cortisol are associated with Depression (Brody Preut, Schommer, and Schurmeyer, 2002). One of the possible mechanisms for the outcome of this is that high levels of cortisol in the brain downregulate 5-HT receptors (de Kloet, Sybesma and Reul, 1986), and may also reduce the availability of tryptophan ( Maes, De Ruyter, Hobin and Suy, 1987), which is essential for the synthesis of serotonin.

Stress can release neuropeptides that can induce brain mast cells release histamine, causing an allergic reaction Th2 (Abbas, Lichtman, and Pober, 2000). Histamine stimulates the HPA axis, without the activation of serotonergic and adrenergic receptors. A proposed mechanism for the effect described above is histamine, which interacts with prostaglandin to stimulate the HPA axis (Willems et al., 1999). The hormone corticosterone increases the levels of histamine in the hypothalamus, and excess histamine, which in turn increases the plasma levels of corticosterone (Mazurkiewicz-Kwilecki, 1983), providing a 'feed-forward loop that may contribute to a HPA axis dysfunction.

Some peptides that stimulate the release of CRF HPA axis hormones can cause a variety of behavioral abnormalities in animals. The anomalies are the reactions of fear, aversion, increased awareness, decreased food intake, stress induced by immobilization, and inhibition of exploration (Koob, 1999). Histamine can cause behavioral abnormalities almost identical, reinforcing the hypothesis that histamine is an important stimulus of CRF release. ACTH is also released by the stimulation of both H1 and H2 receptors (Knigge and Warberg, 1991).

As mentioned above, the release of histamine increases the levels of Ca2 + through IP3. It seems that many mental patients have elevated Ca2 + responses (Kusumi and Koyama, 1998). There is evidence that there is an increase of calcium released during aging (Kurian, Chandler, Patel, and crew, 1992), which may explain some age-related dementias. Some doctors believe that Depression can be caused by hypofunction of cAMP-mediated cellular responses and pathways IP3/DAG domain, whereas the opposite is true for mania (Wachtel, 1990). The correlation between low levels of field, with depression and high levels of cAMP mania has resulted so far in 1970 (Abdulla & Hamadah, 1970). The regulation of the enzyme phosphodiesterase degradation of cAMP. Importantly, the phosphodiesterase inhibitor Rolipram has antidepressant activity (Wachtel, 1982). Thus, histamine may be involved in depression or mania, depending on the path has a greater influence on the receiver.

The following discussion is an example of a model for regulation of the receptor cell. Low levels of serotonin causes the brain to adapt to the increased number of serotonin receptors, called 'up-regulation ". Many if not all, of the downstream of small molecules and proteins in the street are up-regulated, including the density of serotonin receptors (Arora and Meltzer, 1989). The problem is that any changes in serotonin levels will be amplified by way of Now Up-regulation. In theory, this can lead to mood swings, bipolar disorder, anxiety, major depression and maybe (Aprison, Takahashi, and tachikata, 1978), presumably due to 'burnout' path overwork. Selective inhibitors of serotonin reuptake (SSRIs — Prozac, Zoloft, Paxil, Luvox, Celexa, Lexapro) are designed to alleviate depression by normalizing the path to the serotonin-regulated. They block the reuptake of serotonin in the axon, thus keeping more in the synapse. More of serotonin in the synapses means that more binds to receptors for serotonin. Previously receptor is regulated until then regulated down to normal levels, and the path through the receptor becomes down-regulated, and then normalized. The same effect was observed with the inhibitor of norepinephrine reuptake Effexor to camp. Since histamine can inhibit the function of serotonin receptors can cause mental illness directly through the mechanism described above for the route to regulation.

There is ample evidence that the street names is important in the maintenance of synaptic plasticity (mental health). Long-term antidepressant results in the activation of PKA (Popoli, Brunello, Perez, & Racagni, 2000). Several types of inhibitors of serotonin and norepinephrine reuptake (antidepressants), increasing the level of CREB mRNA (NIBU, Nestler and Duman, 1996). The non-pharmaceutical antidepressant S-SAM (SAM) has stimulated the field to join the PKA, and also increased the activation by phosphorylation map2 (Zanotti et al., 1998). As mentioned above, the H2 receptor activated by cAMP.

Histamine stimulates neuronal firing through H1 receptors, whereas the H2 receptor activation inhibits neuronal firing (Jacobs, Yamatodani and Timmerman, 2000). As mentioned above, the location of the H1 receptor is IP3/DAG. The IP3/DAG molecule PIP2 signaling pathway is significantly higher in mania (Brown, Mallinger, Renbaum, 1993). The route of the DAG PKC enzyme is high in mania compared with normal subjects (Friedman et al., 1993). The administration of antidepressants decreases in vitro in cytosolic Ca2 + release (Ca2 + activation) (Shimizu et al., 1994), and can also inhibit protein kinase Ca 2 + pathway (Silver, Sigg, and Moyer, 1986). However, the activation of some Ca 2 +-dependent protein kinases (eg CaM KII) increased levels of BDNF expression (Ghosh, Carnahan, and Greenberg, 1994).

The above findings underline the theory that IP3/DAG path can be both positive and negative synaptic plasticity, which is the mobile mental health related. One theory is that low levels of Ca2 + release lead to synaptic depression, whereas large Ca2 + increases the opposite effect (Lisman, 1994). Another explanation of how the road can be unbalanced IP3/DAG is that some neurotransmitters may stimulate signaling through one way or another. There is some evidence to support this theory. In one study, metabolic modified products of IP3 and DAG were measured after stimulation with neurotransmitters different path. Serotonin is balanced and the metabolic response DAG IP3, while the response of histamine is a weak DAG, but a strong IP3 response metabolite (Sarri, croutons, and Claro, 1995). As mentioned above, there is much evidence to suggest that the DAG path promotes mental health, while the IP3 pathway can cause mental illness. Both routes mentioned above are activated by H1 receptors.

It is possible that Ca2 + (IP3/DAG) and Camp and PKA pathways may antagonize each other (Jacobs, Yamatodani and Timmerman, 2000). In fact, there is much evidence suggesting a direct antagonism between cAMP and IP3 pathways (DAG feeds via cAMP, and should not be included in the antagonism by cAMP). As mentioned above, serotonin activates the street through IP3 binding to its receptors 5-HT2A. Serotonin-stimulated release of Ca2 + was significantly higher in severe depression, melancholia, call (Kusumi, Koyama and Yamashita, 1991), although the signal serotonin maneuver through camp is the alleged mechanism of antidepressant action. Histamine stimulates the formation of IP3 (Bielkiewicz-Vollrath, Carpenter, Schulz, and Cook, 1987). As discussed in the preceding paragraph, the CAM is a protein downstream of IP3. CaM activates the enzyme phosphodiesterase that degrades cAMP (Cheung, 1970), damaging the critical path. In contrast, activation of PKA inhibits CaMKII many (Matsushita & Nairn, 1999), as mentioned above CaMKII are immediately downstream of the CAM in the IP3 path. In addition, some antidepressants have been shown to inhibit the CAM (Silver, Sigg, and Moyer, 1986).

As mentioned above, calcineurin is IP3. Calcineurin inhibition can cause anxiety for the release, the major inhibitory neurotransmitter, GABA (Klee, Ren & Wang, 1998). Calcineurin pathway also negatively regulates the CREB protein, cAMP, presumably by increased degradation (Bito, Deisseroth and Tsien, 1996). A study has shown that CREB activates calcineurin, but that was in the pancreatic islet cells, not in the central nervous system (Schwaninger et al., 1995). Other studies have shown that normally inhibits the activity of PKA protein calcineurin inactivation of PKA downstream targets (substrates) (Shenolikar & Nairn, 1991; Greengard et al., 1998). Inhibits calcineurin, an important form of synaptic plasticity known as long-long-term potentiation (LTP), which often leads to long-term term depression (LTD) (Winder et al., 1998). The enzyme calcineurin and cAMP-PKA pathway antagonize each other in the regulation of various downstream proteins that CREB (Tong, Shepherd & Jahr, 1995; Raman, Tong & Jahr, 1996; Traynelis & Wahl, 1997). Perhaps more important, calcineurin is activated during allergic reactions (Abbas, Lichtman, and Pober, 2000).

The H1 receptor stimulates IP3/DAG way, and is also the receptor that is involved in allergic reactions (Repka-Ramirez & Baraniuk, 2002). The central nervous system, activation of H1 receptors can inhibit learning and memory (Knoche et al., 2003). Histamine injected into mice initially resulted in hypoactivity followed by hyperactivity, these effects were abolished by the addition of an H1 block (antagonist) (Chiavegatti, hake, and Bernardi, 1998). H1 antagonists also inhibits histamine-induced increase in spontaneous motor activity in rats (Kalivas, 1982). The mutant mice that have had their hit H1-receptor responses has eased out of aggression against intruders of animals compared with normal mice (Yanai et al., 1998a). This suggests that the H1 receptor is involved in aggressive behavior. H1 knockout mice had a marked increase in serotonin levels (Yanai et al., 1998b). This effect might simply be the serotonin system to compensate for the lack of H1 receptor stimulation. Furthermore, the effect of this might suggest that the strength of H1 receptor activation results in low levels of serotonin, and perhaps later anxiety and depression symptoms.

Human beings have a certain mutation of the H2 receptor "had a greater susceptibility to schizophrenia" (Brown, Stevens, & Haas, 2001, p. 647). Moreover, it appears that the histamine-induced depression may be mediated through H2 receptors, although the H2 receptor activation increases cAMP levels. In animal models, administration of histamine often have a depressive effect, which can be reversed by the H2 receptor blockade, but not to block H1 receptors (Cantu and Korek, 1991). Activation of histamine H2-receptor inhibits the normal immune response that are regulated by vitamin C (Johnston, 1996). As noted above, the H2 receptor activation increases cAMP levels and activated by PKA (Jacobs, Yamatodani, and Timmerman, 2000). Activation of PKA is the theoretical explanation of the action of many antidepressant drugs, especially those that block the reuptake of norepinephrine. However, the increase in cAMP may be denied by the H2 receptor activation of GABA receptors, which then inhibit shoot all serotonergic neurons (Lakoski & Aghajanian, 1983). As mentioned above, serotonin and their receptors play a key role in maintaining mental health. The activation of H2-receptor inhibits neuronal firing in general (Jacobs and Yamatodani Timmerman, 2000), by activating GABA. Although H2 receptor increases levels of cAMP, the final result of the H2 receptor activation is inhibition of other neurotransmitters.

An important role of histamine is the activation of cells that produce stomach acid. Histamine-2 (H2-receptor) antagonists are commonly used as antacids stomach. H2 receptors are also found in the brain. Histamine H2-receptor antagonists may slow the progression of Alzheimer's disease (Lipnik-Stangelj, Juric and Carman-Kržan, 1998). This suggests that in the brain, histamine H2 receptor-mediated activation can cause brain damage. All H2-receptor antagonists in the CNS can cause adverse reactions. The CNS-specific reactions include: "delirium, psychosis, confusion, disorientation, hallucinations, hostility, altered mental status, irritability, drowsiness, or agitation" (Cantu and Korek, 1991, p. 1027). In particular, the H2 antagonist, cimetidine (Tagamet) CNS can have serious side effects, including epileptic phenomena, delirium and coma (Van Sweden and Kamphuis, 1984). In animal studies, H2 antagonists also can be scary (Santos, Huston, and Bandai, 2001).

H3 histamine receptor H1 and H2 receptor regulator negative, inhibiting the release of histamine (Bongers, Leurs, Robertson, and Raber, 2004). Evidence in support of the effects of histamine generation of anxiety comes from the observation that the H3 receptor blockade increases anxiety in animals (Bongers, Leurs, Robertson, and Raber, 2004). However, H3 blockers may also have antidepressant effects (Ito, 2000). Sometimes antidepressants can increase anxiety and the H3 receptor may play an important role in this side-effect medication. The H3 receptor has been implicated in several mental disorders, including migraine, disorder and attention deficit hyperactivity disorder (ADHD), schizophrenia and Alzheimer's disease (Leurs, Bakker, Timmerman, and Esch, 2005). Unlike the three other histamine, H3 receptor can couple to several signal transduction pathways (pass through, et al., 2004). As mentioned above, histamine suppresses food intake. Paradoxically, the knockout mice H3 receptor often become obese (Takahashi, Suwa, Ishikawa, and Kotani, 2002). The H4 receptor was discovered recently. One of his main roles seems to be the activation of mast cells (Hofstra, Desai, Thurmond, & Fung-Leung, 2003).

Increased histamine levels in mice results in increased use of vitamin C and, presumably, synthesis (Nandi, Subramanian, Majumder and Chatterjee, 1974). An interesting experiment was conducted in rats by a research group in India in 1970. When "1 mg of histamine was injected into mice, the increase of histamine in urine was about four times, but returned almost to normal after administration of ascorbic acid (Subramanian, Nandi Majumdar and Chatterjee , 1974, p. 639). In humans, integration with 2000mg/day Vitamin C, histamine levels drop by an average of 40% (Johnston, Retrum and Srilakshmi, 1992). One result of the conduct of teas histamine levels increased appetite. As mentioned above, histamine plays a role in eating behavior, including suppression of food intake and stimulates the intake of animals (Sakata and Yoshimatsu, 1995). It is interesting to note that vitamin C appears to play a positive role in feeding behavior, because low levels of vitamin C in the brain result in decreased appetite (Wilson, 1982).

As mentioned in the introductory section of this chapter, prostaglandins affect brain activity and immune activity. Vitamin C plays a role in the metabolism of prostaglandins, including the breakdown of dihomo-gamma-linolenic acid (DGLA) in secondary metabolites. DGLA becomes normal inflammatory metabolite of arachidonic acid (AA) (Horrobin, 1996). Thus vitamin C plays a role in mediating anti-inflammatory. Vitamin C and prostaglandin E1 (PGE1) can share a similar role in regulating collagen synthesis, infection and cholesterol levels and insulin (Horrobin, 1996). Although histamine plays an important role in Th2 immune response, it is actually recognized as an immunosuppressive agent. Two grams of vitamin C increased the migration of certain immune cells called neutrophils, and this migration is inversely correlated with histamine levels in the blood. This suggests that vitamin C may enhance immune function through histamine detoxification (Johnston, Martin, and CAI, 1992).

Vitamin C detoxifies histamine for conversion to hydantoin-5-acetic acid, aspartic acid, and then (Clemetson, 1999). To achieve this, the vitamin C should be of copper (Cu2 +) as a catalyst to degrade histamine (Sharma and Wilson, 1980). Vitamin C also inhibits the enzyme phosphodiesterase that degrades cyclic AMP. This results in increased cAMP levels (Tisdale, 1975). Moreover, vitamin C synergizes with inducers of cAMP to stimulate cAMP production (Hitomi & Tsukagoshi, 1996). This effect in the field of vitamin C is the second largest anti-histamine action (in addition to the degradation of histamine), because cAMP inhibits the release of histamine (Cathcart, 1986). Cyclic AMP is also a potent inhibitor of allergy IgE stimulated mediator release, including: histamine, slow reacting substance (SRS-A), prostaglandin (PG) and an eosinophil chemotactic factor (ECF-A) " (James and Wilson, 1980, p. 163). Vitamin C also inhibits GF2a prostaglandin (PGF2a) synthesis. PGF2a decreased levels of cAMP. Importantly, the decreased levels of cAMP are associated with histamine release (Mohsenin & Dubois, 1987).

Abstract:

Histamine is a multifunctional hormone excess has potentially lethal side effects. Side effects from lethal allergen overstimulation of the immune system, leading to release of excess histamine, which can reduce blood pressure to the point of impact (Katzung, 1998). Histamine is intimately involved in both immune activity and central nervous system. That affects a number of functions in the CNS, including "excited state, the functions of brain energy metabolism, locomotor activity, neuro-endocrine, autonomic and vestibular food, drink, sexua| behavior, and l analgesia (Wada, Inagaki, Yamatodani and Watanabe, 1991, p. 415). Histamine is formed by amino acid histidine, and is unique among neurotransmitter amino acid derivatives, as it degrades the extracellular space (synapse), instead of being received by the release of the neuron (axons). This is important because the level of vitamin C in the brain plays an important role in how quickly excess histamine is removed from the synapse before it has a morbid after effects. Histamine is an excitatory neurotransmitter, and seems to cause anxiety in some people (Hasenöhrl, Weth, and Huston, 1999).

H1 and H2 receptors are the most important of the four types of histamine receptors. The H1 receptor is coupled to the inositol triphosphate (IP3) / diacylglycerol (DAG) route, and the H2 receptor is coupled through cAMP. Although histamine sends a signal through both excitatory receptors, activation of a street can lead to depression. H1 receptor, this is probably due to activation of calcineurin, a protein involved in long-term depression (LTD) of neurotransmission (Winder et al., 1998). The depression created by the H2 receptor activation is probably due to the inhibition of neuronal firing down (Jacobs, Yamatodani, and Timmerman, 2000). Another theory is that the H2 receptor activation causes inhibition of the serotonergic system (Lakoski & Aghajanian, 1983), which is the purpose of activation of many antidepressants. A third theory is that histamine indirectly causes the depression of the inhibition of the release of other neurotransmitters (Brown, Stevens, & Haas, 2001).

There is evidence that some individuals are much more sensitive to histamine than in others (Katzung, 1998). In addition to anxiety, histamine has also been linked to Attention Deficit Disorder (ADD) (pass through, Bacciottini, Mannion, and Blandina, 2000) and alcoholism (Lintunen, et. Al, 2002). , The major inhibitory neurotransmitter in the brain, gamma-amino butyric acid (GABA), inhibits histamine release (Jacobs and Yamatodani Timmerman, 2000), suggesting that control of histamine levels in the brain is important . Many of the anti-anxiety drugs affect the GABAergic system.

Histamine can activate the hypothalamic-pituitary-adrenal (HPA), the main neuroregulatory system in the body. Normally the neurotransmitters dopamine, serotonin, norepinephrine, control and release of a key hormone of the HPA axis, corticotropin-releasing factor (CRF) (Tuomisto & Mannisto, 1985). Given that histamine inhibits the release of neurotransmitters mentioned above, can unbalance the HPA axis through overstimulation. Chronic stimulation of the HPA axis can lead to depression (Hurwitz & Morgenstern, 2001). Histamine release another key HPA axis adrenocorticotropic hormone (ACTH) (Knigge and Warberg, 1991), which is directly downstream of the IRC.

We assume that the DAG path generally plays a positive role in mental health, while the IP3 path can play a negative role (Wachtel, 1990). Interestingly, histamine has strong potential to stimulate the activities of IP3 and DAG stimulation, a weak activity (Sarri, croutons, and Claro, 1995). Of calcium ions (Ca2 +) is released after activation of the IP3 path. Studies have shown that the release of Ca2 + is greater in major depression (Kusumi, Koyama and Yamashita, 1991). Calcineurin protein is downstream of the release of Ca2 +. As mentioned above, calcineurin is a neurotransmitter involved in depression. Histamine and calcineurin are involved in mental illnesses and allergic reactions (Abbas, Lichtman, and Pober, 2000) and therefore the activation of histamine in calcineurin may play a key role in both these morbid results.

Further evidence of the potential morbidity of the track is that the activation of IP3 receptors H1 can inhibit learning and memory (Knoche et al., 2003), causes hyperactivity (Chiavegatti, hake, and Bernardi, 1998), l " ; case of assault (Yanai et al., 1998). An H2-receptor mutation may lead to schizophrenia (Brown, Stevens, & Haas, 2001). Some antihistamines can reduce anxiety by the H1 receptor antagonism (Lader and Scotto, 1998), while H2 antagonists may have antidepressant effects (Cantu and Korek, 1991). Both H1 and H2 antagonists may cause a variety of physical and mental side effects.

Had increased levels of histamine in the increased use of vitamin C (Nandi, Subramanian, Majumder and Chatterjee, 1974), suggests that vitamin C regulates the levels of histamine through its antihistamine effect. Vitamin C is a very effective detoxifying histamine (Clemetson, 1999). "After two weeks of 2,000 mg of vitamin C per day, the level of histamine in the blood decreased by about 40% below the reference value" (Johnston, Retrum and Srilakshmi, 1992, p. 989). Vitamin C increases the cAMP level (Tisdale, 1975), a key molecule in improving mental health through cAMP. Perhaps equally important, cAMP inhibits the release of histamine (Cathcart, 1986). In contrast, low levels of cAMP can increase the release of histamine (Mohsenin & Dubois, 1987).