And neuromodulators

Nitric Oxide. Nitric oxide [10102-43-9] NO, is a ubiquitous intracellular and intercellular messenger serving a variety of functions including vasodilation, cytotoxicity, neurotransmission, and neuromodulation (9). NO is a paramagnetic diatomic molecule that readily diffuses through aqueous and hpid compartments. Its locus of action is dictated by its chemical reactivity and the local environment. NO represents the first identified member of a series of gaseous second messengers that also includes CO. 

The pharmacodynamic effects of ethanol are complex, and any attempt to link its actions to specific neurotransmitters or isolated brain regions is simplistic. A complicated neural network involved in the actions of ethanol accounts for its reinforcing, intoxicating, and abstinence effects. At the present time, use of medications that target neurotransmitters and neuromodulators affected by ethanol represents a reasonable strategy for the development of pharmacotherapies that reduce the reinforcing effects of alcohol and the craving and withdrawal symptoms that commonly occur in the context of alcohol dependence. 

Lauro C, Di Angelantonio S, Cipriarri R et al (2008) Activity of adenosine receptors type 1 is required for CX3CLl-mediated neuroprotection and neuromodulation in hippocampal neurons. J Immunol 180 7590-7596... 

Baghdoyan, H. A. Lydic, R. (2002). Neurotransmitters and neuromodulators regulating sleep. In Sleep and Epilepsy The Clinical Spectrum, ed. C. W. Bazil, pp. 17 44. New York, NY Elsevier Science. 

Sakai, K. (1985). Neurons responsible for paradoxical sleep. In Sleep Neurotransmitters and Neuromodulators, ed. A. Wauquier and Janssen Research Foundation. 

Pace-Schott, E. F. Hobson, J. A (2002). Basic mechanisms of sleep New evidence on the neuroanatomy and neuromodulation of the NREM-REM cycle. In Neuropharmacology - The Fifth Generation of Progress, ed. D. Charney and C. Nemeroff, pp. 1859-77. Philadelphia, PA Lippincott Williams and Wilkins. 

Neuropeptide A family of neurotransmitters and neuromodulators comprised of unique sequences of amino acids. 

Various experimental criteria are used to formally differentiate among hormones, neurotransmitters and neuromodulators. However, for behavior it often is difficult to discriminate among these categories of function, since a given chemical compound may act at several locations and have more than one mode of action (Brown, 1994). For the pur-... 

Figure 8.18 The role of the intestine and kidney in formation of arginine. The intestine converts arginine to citruUine, to be released into the blood to be taken up by the kidney where it is converted to arginine. An important role of arginine is conversion to nitric oxide, a key messenger molecule, and neuromodulator in the brain (Chapter 14).

There is now evidence that the mammalian central nervous system contains several dozen neurotransmitters such as acetylcholine, noradrenaline, dopamine and 5-hydroxytryptamine (5-HT), together with many more co-transmitters, which are mainly small peptides such as met-enkephalin and neuromodulators such as the prostaglandins. It is well established that any one nerve cell may be influenced by more than one of these transmitters at any time. If, for example, the inhibitory amino acids (GABA or glycine) activate a cell membrane then the activity of the membrane will be depressed, whereas if the excitatory amino acid glutamate activates the nerve membrane, activity will be increased. The final response of the nerve cell that receives all this information will thus depend on the balance between the various stimuli that impinge upon it. 

A summary of the neurotransmitters and neuromodulators that have been identified in the mammalian brain is given in Table 2.1. The term neuromodulator is applied to those substances that may be released with a transmitter but which do not produce a direct effect on a receptor a neuromodulator seems to work by modifying the responsiveness of the receptor to the action of the transmitter. 

Table 2.1. Some of the neurotransmitters and neuromodulators that have been identified in the mammalian brain...

The neuropeptide CCK is an octapeptide found regionally in the gastrointestinal tract and brain (brain-gut peptide), where it acts as a neurotransmitter and neuromodulator. Its most abundant form in the brain is the C-terminal sul-fated octapeptide fragment CCK-8, which interacts with the same affinity with both CCK receptor subtypes CCK-A and CCK-B. Extensive pharmacological studies have been carried out during the past few years suggesting that CCK may participate in the neuroendocrine responses to stress (e.g., Harro et al. 1993 Dauge and Lena 1998). 

The innervation of the gastrointestinal tract is complex. The myenteric and submucosal plexuses contain many interneurons. These possess a number of neurotransmitters and neuromodulators, including several peptides, such as enkephalins, substance P, and vasoactive intestinal peptide. Reflex activity within the plexuses regulates peristalsis and secretion locally. The effects of sympathetic and parasympathetic nerve stimulation are superimposed on this local neural regulation. 

All of the opioid agonists produce some degree of tolerance and physical dependence. The biochemical mechanisms underlying tolerance and physical dependence are unclear. It is known, however, that intracellular mechanisms of tolerance to opioids include increases in calcium levels in the cells, increased production of cAMP, decreased potassium efflux, alterations in the phosphorylation of intracellular and intranuclear proteins, and the resultant return to normal levels of release of most neurotransmitters and neuromodulators. Tolerance to the analgesic effects of opioids occurs rapidly, especially when large doses of the drugs are used at short intervals. However, tolerance to the respiratory depressant and emetic effects of the opioids occurs more slowly. The miotic and constipative effects of the opioids rarely show tolerance. 

The third part. Developmental Psychopathology, delves into detailed disease-specific overviews. Each of the chapters covers issues pertaining to nosology and classification, to genetic determinants, brain systems implicated, environmental influences, and nature-nurture interactions. Neurotransmission and neuromodulation, and hormonal and other developmental influences are addressed and, whenever available, relevant animal models are incorporated into the discussion. The interplay of normative and derailed development is a core concept for these chapters. Of the part s 12 chapters, 9 are devoted to traditionally defined disease categories, and 3 cover the overarching areas of early-life stress, aggression, and affiliative behaviors. 

Histamine was synthesized in 1907 and later isolated from mammalian tissues. Early hypotheses concerning the possible physiologic roles of tissue histamine were based on similarities between the effects of intravenously administered histamine and the symptoms of anaphylactic shock and tissue injury. Marked species variation is observed, but in humans histamine is an important mediator of immediate allergic (such as urticaria) and inflammatory reactions, although it plays only a modest role in anaphylaxis. Histamine plays an important role in gastric acid secretion (see Chapter 62) and functions as a neurotransmitter and neuromodulator (see Chapters 6 and 21). Newer evidence indicates that histamine also plays a role in chemotaxis of white blood cells. 

---