Neuromodulator

The distinction between neuromodulator and neurotransmitter is sometimes difficult to define (7,8). Generally, however, the primary function of a... 

CGRP is widely distributed throughout the peripheral and central nervous systems and is found ia sensory neurons and ia the autonomic and enteric nervous systems. In many iastances CGRP is co-localized with other neuroregulators, eg, ACh ia motor neurons, substance P, somatostatin, vasoactive intestinal polypeptide (VIP), and galanin ia sensory neurons. It is also present ia the CNS, with ACh ia the parabigeminal nucleus and with cholecystokinin (CCK) ia the dorsal parabrachial area. CGRP functions as a neuromodulator or co-transmitter. 

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. 

SRIF acts as an excitatory neuromodulator in the CNS inhibiting the release of TRH, corticotropin-releasing hormone (CRH), growth hormone releasing factor (GHRH), and NE. It produces general arousal and hypotension. It inhibits the release of a number of peptides and modulators in the GI tract. 

As a neurotransmitter in the sensory nervous system, high levels of substance P are found in the dorsal horn of the spinal cord as well as in peripheral sensory nerve terminals. However, substance P also plays a significant role as a neuromodulator in the central, sympathetic, and enteric nervous system. NKA and NKB are also localized selectively in the CNS. 

It is important to point out that some types of placebo analgesia appear to be insensitive to naloxone, thus suggesting that neuromodulators other than opioids can be involved in some circumstances. For example, if a placebo is given after repeated administrations (preconditioning) of the non-opioid painkiller ketorolac, the placebo analgesic response is not blocked by naloxone. 

Purinergic System. Figure 2 Schematic of sympathetic cotransmission. ATP and NA released from small granular vesicles (SGV) act on P2X and a-i receptors on smooth muscle, respectively. ATP acting on inotropic P2X receptors evokes excitatory junction potentials (EJPs), increase in intracellular calcium ([Ca2+]j) and fast contraction while occupation of metabotropic ar-adrenoceptors leads to production of inositol triphosphate (IP3), increase in [Ca2+]j and slow contraction. Neuropeptide Y (NPY) stored in large granular vesicles (LGV) acts after release both as a prejunctional inhibitory modulator of release of ATP and NA and as a postjunctional modulatory potentiator of the actions of ATP and NA. Soluble nucleotidases are released from nerve varicosities, and are also present as ectonucleotidases. (Reproduced from Burnstock G (2007) Neurotransmission, neuromodulation cotransmission. In Squire LR (ed) New encyclopaedia of neuroscience. Elsevier, The Netherlands (In Press), with permission from Elsevier). 

A neuromodulator that is released from the post-synaptic neuron and acts at the pre-synaptic neuron that makes a... 

Berry MD (2004) Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators. J Neurochem 90 257—271... 

Biocatalysis has emerged as an important tool for the enantioselective synthesis of chiral pharmaceutical intermediates and several review articles have been published in recent years [133-137]. For example, quinuclidinol is a common pharmacophore of neuromodulators acting on muscarinic receptors (Figure 6.50). (JJ)-Quinudidin-3-ol was prepared via Aspergillus melleus protease-mediated enantioselective hydrolysis of the racemic butyrate [54,138]. Calcium hydroxide served as a scavenger of butyric acid to prevent enzyme inhibition and the unwanted (R) enantiomer was racemized over Raney Co under hydrogen for recycling. 

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. 

The POMC family consists of peptides that act as hormones (ACTH, LPH, MSH) and others that may serve as neurotransmitters or neuromodulators (endorphins) (see Figure 42-15). POMC is synthesized as a precursor molecule of 285 amino acids and is processed differ-endy in various regions of the pituitary. 

Fig. 8.3 Chemokines are neuromodulators. Some chemokines can be synthesized, as their own receptor, by the same neuron (a). A chemokine released by exocytosis can modulate the electrical activity of neurons after binding to its own presynaptic receptor (autoreceptor). Chemokines can also act on other neurons and glial cells (astrocytes and microgha) which express chemokine receptors (b). (Adapted from Rostene and Melik-Parsadaniantz, Pour la Science 2008, 369 66-72)...

Rostene W, Kitabgi P, Parsadaniantz SM (2007) Chemokines a new class of neuromodulator Nat Rev Neurosci 8 895-903... 

Jung H, Toth PT, White FA, Miller RJ (2008) Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons. J Neurochem 104 254-263... 

---