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Complement peptides and neuronal dysfunction in the central nervous system: Specificity of receptor sites for anaphylatoxin C3a activity in the rat hypothalamus
Author(s) -
Williams Curtis A.,
Schupf Nicole,
Reilly Christopher L.,
Wagner Jolynn
Publication year - 1988
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430150210
Subject(s) - anaphylatoxin , complement system , receptor , chemistry , endocrinology , hypothalamus , arginine , medicine , immune system , biology , biochemistry , immunology , amino acid
The research described centers on the possible activities of complement in neural tissues. Activation of the complement cascade will generate the pharmacologically potent anaphylatoxins C3a and C5a, cleavage peptides of C3 and C5, respectively. Their actions depend on a carboxyterminal arginine, and they are inactivated by a carboxypeptidase in serum, yielding the desarginated derivatives C3ai and C5ai. Using well‐characterized eating and drinking responses to focal chemical stimulation of hypothalamic sites in the rat, we have shown that immune complex formation elicits consummatory behaviors which mimic the responses to norepinephrine (NE) and dopamine (DA). We have also shown these effects to be complement dependent. C5a was found to stimulate eating, similar to the effect of NE, and C3a was found to mimic the effect of DA, potentiating NE‐induced eating or carbachol‐induced drinking. C5a has been shown to act presynaptically to modulate endogenous catecholamine function. In this study 125 ‐C3a binding to a refined synaptosome preparation reveals a C3a binding site which is completely inhibited by C3ai. We also show that the psychopharmacological action of C3a is also antagonized by C3ai. These studies demonstrate the presence of anaphylatoxin‐sensitive sites in the perisynaptic membrane systems of the rat CNS. They also suggest that the anaphylatoxins could mediate or contribute to the neuropsychiatric disorders often seen in immune complex disease.