Histamine central functions

Histamine immunoreactive neurons have been identified in the tuberal region of the posterior hypothalamus (tuberomammilary nucleus), projecting to nearly all parts of the brain. Three histamine receptors are known histamine-related functions in the central nervous system (CNS) are regulated at postsynaptic sites by the H and H2 receptors, while the H3 receptor exhibits the features of a presynaptic autoreceptor, mediating the synthesis and release of histamine. The Hi receptor is widely distributed in the CNS. It is present in all areas and layers of the cerebral cortex, limbic system, caudate putamen, nucleus accumbens, thalamus, hypothalamus, mesencephalon, and lower brainstem and spinal cord. The H2 and H3 receptors are also distributed extensively and in a heterogeneous fashion in the CNS. Regarding the role of histamine in the CNS, there is substantial evidence that it plays a role in control of the sleep/wake cycle. Whether the... 

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

Histamine is a biogenic amine that is widely distributed in the body and functions as a major mediator of inflammation and allergic reactions, as a physiological regulator of gastric acid secretion in the stomach, as a neurotransmitter in the central nervous system (CNS) and may also have a role in tissue growth and repair. 

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

Although histamine is not stored in neurons outside of the central nervous system, mast-cell-derived histamine can modify peripheral sensory nerve function. Both acute and chronic pain states can result from inflammation or peripheral nerve cell injury, and there is substantial evidence that mast cell histamine participates in these disorders. 

The neurotransmitter histamine (HA) exerts several functions in the hypothalamus [1-2] including an involvement in the neuroendocrine regulation of pituitary hormone secretion [3]. HA has no effect directly at the level of the pituitary gland, but influences the secretion of anterior pituitary hormones either by an exerted e.g. in the paraventricular nucleus (PVN) on other central transmitters or hypothalamic regulating factors, which subsequently regulate the release of anterior pituitary hormones. In addition, HA acts on the supraoptic nucleus (SON) in the hypothalamus where the posterior pituitary hormones are synthesized and thereby exerts a direct effect on the release of the posterior pituitary hormones. Immunohistochemical studies have revealed that the histaminergic neurons, which originate in the tuberomammillary nuclei of the posterior hypothalamus, densely innervate most of the hypothalamic areas involved in the neuroendocrine control of pituitary hormone secretion [4-5]. Within the last two decades the effect of HA on pituitary hormone secretion have been explored in several studies and it has been... 

Additionally, cardiac function can also be modulated by centrally-located H3-receptors. The intracerebroventricular administration of (R)a-methylhistamine in conscious animals is associated with a marked reduction of the heart rate, an effect which is antagonised by thioperamide (McLeod et al., 1991). The peripheral administration of ipratropium, a muscarinic antagonist which does not cross the blood-brain barrier, prevents such inhibition, demonstrating that the activation of centrally-located histamine H3-receptors leads to an increase in the vagal tone to the heart, rather than to a facilitatory effect on the sympathetic efferent fibers. 

McLeod, R.L., Gertner, S B., Hey, J.A., 1991. Modulation of cardiovascular function by central histamine H3 receptors in conscious guinea pigs. Eur. J Pharmacol. 206, 141-142. 

Histamine is not only a mediator of several (patho)physiological actions, but also functions as a neurotransmitter, both centrally as peripherally [1, 2]. Feedback mechanisms are crucial to neurotransmission and the presynaptic histamine H3 receptor not only plays a key role in regulating histamine release but also regulates the release of other neurotransmitters (for further details see chapter 2 and 3). Because inhibitory effects on histamine H3 receptor-mediated stimuli by G protein toxins (both cholera and pertussin toxin) have been reported, it is most likely that the histamine H3 receptor also belongs to the superfamily of G protein-coupled receptors [3,4], i.e. coupled to a G protein of the Gi/0 class [5]. The reader is referred to chapter 6 for more details. 

Gothert M, Garbarg M, Hey JA, Schlicker E, Schwartz JC, Levi R (1995) New aspects of the role of histamine in cardiovascular function identification, characterization, and potential pathophysiological importance of H3 receptors. Can J Physiol Pharmacol 73 558-64 Gothert M, Fink K, Frolich D, Likungu J, Molderings G, Schlicker E, Zentner J (1996) Presynaptic 5-HT auto- and heteroreceptors in the human central and peripheral nervous system. Behav Brain Res 73 89-92... 

Histamine is both a local hormone and a neurotransmitter in the central nervous system. It is synthesized in neurons and mast cells. There are Hi, H2, and H3 receptors in the central nervous system, but they differ in their localization, biochemical machinery, functions, and affinities for histamine they are particularly important in maintaining a state of arousal or awareness (1). 

In Chapter 1, the structure, synthesis and toxicity of ricin, a protein present in the endosperm cells of the seeds of the castor oil plant, are described and possible uses of this toxic agent in immunology as conjugates with antibodies are discussed. The biochemical and pharmacological evidence for the presence of functional histamine receptors in the mammalian central nervous system is set out in Chapter 2. Chapter 3 covers the chemical properties of molybdenum-containing enzymes such as aldehyde oxidase and xanthine oxidase, although their physiological roles are by no means clear. 

Perphenazine is thought to exert its antipsychotic effects by postsynaptic blockade of CNS dopamine receptors, thus inhibiting dopamine-mediated effects. The antiemetic effects of perphenazine are attributed to dopamine-receptor blockade in the medullary chemoreceptor trigger zone. Perphenazine has many other central and peripheral effects it produces both alpha and ganglionic blockade and counteracts histamine- and serotonin-mediated functions. It produces... 

Sensory nerves contain no acetylcholine and the chemical mediator involved in the simplest unit of central nervous activity, the monosynaptic reflex, is not known. For this reason, some considerable attention has been paid to the pharmacological activity of extracts of sensory nerves, which have been shown to contain three substances of potential neuropharmacological significance—ATP, substance P (a polypeptide) and histamine. They have been reviewed at length elsewhere and little need be added here, since it now seems likely that neither ATP nor substance P will be shown to have neurohumoral functions. However, some psychotropic drugs have antihistamine activity and a brief statement is therefore necessary concerning the present status of histamine. 

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