vasoactive-intestinal-peptide and Fatigue-Syndrome--Chronic

Autoimmune dysfunction of certain vasoactive neuropeptides may be implicated in a range of disorders associated with fatigue like states (chronic fatigue syndrome, Gulf War syndrome) and even sudden infant death syndrome. These substances have neurotrophic, neuroregulatory, and neurotransmission functions, as well as that of immune modulators and hormones. They exert significant control over carbohydrate and lipid metabolism. The hypothesis is that because these substances have vital and indispensable roles in cellular processes, loss or compromise of these roles would lead to predictable and severe cellular and systemic effects. The important roles of certain VNs make them a vulnerable target for autoimmune dysfunction. They are known to be associated with heat shock proteins for intracellular functioning with which they may form immunostimulating complexes. While peptide-HSP complexes are a relatively new area for research, this paper asserts that attention could be focused on these substances and complexes in an effort to elucidate a number of perplexing fatigue-associated disorders.

Topics: Autoimmune Diseases; Autoimmunity; Fatigue; Fatigue Syndrome, Chronic; Heat-Shock Proteins; Humans; Infant, Newborn; Models, Immunological; Neuroimmunomodulation; Neuropeptides; Persian Gulf Syndrome; Sudden Infant Death; Vasoactive Intestinal Peptide

Vasoactive neuropeptides such as pituitary adenylate cyclase activating polypeptide (PACAP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) have been implicated in a number of fatigue-related conditions. Associations of these vasoactive neuropeptides with heat shock proteins (hsps) and cytosine-guanosine dinucleotide (CpG) DNA fragments in autoimmune phenomena have been postulated to interfere with receptor signal activation for adenylate cyclase and other vital cellular processes. However, a specific mechanism for receptor dysfunction has not been explored to date. G protein-coupled receptors (GPCRs) constitute a high proportion of biological receptor mechanisms and serve a wide range of substances including nucleosides, nucleotides, catecholamines, calcium, histamine, serotonin and prostaglandins. They are complex transmembrane hepta-helical serpentine structures with specific binding capabilities resulting in conformational changes that activate cognate cyclic GMP (G proteins). GPCRs adapt to certain stimuli through desensitisation and changes in phosphorylation and are subject to distortions of signalling processes. Hence, these vital signalling structures are susceptible to impairment of function through a range of mechanisms. One of their vital functions is signalling through adenylate cyclase, a vital step in cyclic AMP metabolism. This step involves ATP metabolism and therefore is a crucial mediator of cellular energy pathways. Some GPCRs act to inhibit adenylate cyclase (Gi proteins). Also vasoactive neuropeptides, such as PACAP display a number of receptor isotypes including null variants. Overexpression of Gi proteins and null variant receptors may account for major disruptions of signal transduction and ATP/cAMP metabolism. This paper examines the possible role of GPCR dysfunction in contributing to fatigue-related vasoactive neuropeptide autoimmune disorders which may include chronic fatigue syndrome (CFS), Gulf War syndrome (GWS) and even sudden infant death syndrome (SIDS).

Topics: Adenosine Triphosphate; Adenylyl Cyclases; Autoimmune Diseases; Calcitonin Gene-Related Peptide; Cyclic AMP; Fatigue Syndrome, Chronic; Genetic Variation; Humans; Infant; Models, Biological; Nerve Growth Factors; Neuropeptides; Neurotransmitter Agents; Oligopeptides; Persian Gulf Syndrome; Pituitary Adenylate Cyclase-Activating Polypeptide; Protein Conformation; Protein Structure, Secondary; Receptors, G-Protein-Coupled; Sudden Infant Death; Vasoactive Intestinal Peptide