Multiple roles of neurotransmitters

Chemical transmission between nerve cells involves multiple steps 167 Neurotransmitter release is a highly specialized form of the secretory process that occurs in virtually all eukaryotic cells 168 A variety of methods have been developed to study exocytosis 169 The neuromuscular junction is a well defined structure that mediates the presynaptic release and postsynaptic effects of acetylcholine 170 Quantal analysis defines the mechanism of release as exocytosis 172 Ca2+ is necessary for transmission at the neuromuscular junction and other synapses and plays a special role in exocytosis 174 Presynaptic events during synaptic transmission are rapid, dynamic and interconnected 175... 

The dopamine beta-hydroxylase (Dbh) gene is necessary for the production of NE and epinephrine. Disruption of this gene results in the absence of NE and epinephrine production and is therefore used in studies determining the roles of these neurotransmitters. This approach is favored over the knockout of adrenergic receptors because of the multiplicity of receptor types for NE and epinephrine. 

In the 20 years since Daly reported the potential of adenosine receptors as drug targets (Daly, 1982), considerable advances have been made in the field of purinergic receptor-related research. Although a range of neurotransmitters is known, today there is no doubt that adenosine and adenosine 5 -triphosphate (ATP) also play an important role in the process of cell to cell communication. This function leads to multiple potential indications for research on adenosine and ATP, e.g. neurodegeneration or cardiovascular diseases, but here the focus lies on adenosine s role in pain (see also review by Salter and Sollevi, 2001). 

Calakos N, Schoch S, Siidhof TC et al (2004) Multiple roles for the active zone protein RIMlalpha in late stages of neurotransmitter release. Neuron 42 889-96 Calvert PD, Strissel KJ, Schiesser WE et al (2006) Light-driven translocation of signaling proteins in vertebrate photoreceptors. Trends Cell Biol 16 560-8 Capogna M, Gahwiler BH, Thompson SM (1996) Presynaptic inhibition of calcium-dependent and -independent release elicited with ionomycin, gadolinium, and alpha-latrotoxin in the hippocampus. J Neurophysiol 75 2017-28... 

Regulation of homocysteine metabolism appears to be especially important in the central nervous system, presumably because of the critical role of methyl transfer reactions in the production of neurotransmitters and other methylated products. It has been known for decades that mental retardation is a feature of the genetic diseases, such as CBS deficiency, that cause severe hyperhomocysteinemia and ho-mocystinuria. Impaired cognitive function is also seen in pernicious anemia, which causes hyperhomocysteinemia due to deficiency of cobalamin (see Chapter 28). Hyperhomocysteinemia also may be linked to depression, schizophrenia, multiple sclerosis, and Alzheimer s disease. The molecular mechanisms underlying these clinical associations have not yet been delineated. 

Peptide neurotransmitters and hormones are collectively termed neuropeptides. Neuropeptides typically consist of small peptides of approximately 3 0 residues. Several neuropeptides and several of their regulatory functions are listed these neuropeptides and others function in multiple roles as physiological regulators (too numerous to hst in this short table). Ahhreviations are adrenocorticotropin hormone (ACTH), a-melanoc)de stimulating hormone (a-MSH), neuropeptide Y (NPY), and pituitary adenylate cyclase-activating peptide (PACAP). 

Glutamate s role as a neurotransmitter in the vertebrate retina is reviewed by Barnstable (1993), Brandstatter et al. (1998) and Lo et al. (1998). As the cell bodies of different retinal cell types are in different laminae (Fig. 10), we can assign which general cell types express which glutamate receptor subunits. However, there are different subsets of the same cell class, e.g., there are at least 10 different types of on- and off-bipolars, and multiple subtypes of the other cell classes (Stevens, 1998). Without cell-type markers and double-labelling studies, ISH can not differentiate these. The cones and rods release glutamate onto the bipolar cells only off-bipolars use ionotropic receptors at this synapse on-bipolars use the metabotropic receptor mGluR6 instead. The distribution of NMDA and non-NMDA receptor mRNAs in the retina is summarized in Fig. 10. 

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