ACTH and brain membrane phosphorylation: a model for modulation by neuropeptides.
It has been hypothesized that changes in the phosphorylation of synaptic membrane constituents (proteins and lipids) may affect transmission in certain types of synapses. In this paper some of the recent evidence that neuropeptides like ACTH may bring about their behavioral activity by influencing brain protein and lipid phosphorylation is reviewed. An ACTH-sensitive, cAMP-independent protein kinase was isolated from rat brain synaptosomal plasma membranes. This enzyme was partially characterized and it was observed that its activity greatly depended on the presence of calcium ions. One of its substrate proteins B-50 (MW 48,000; IEP 4.5) may play a key role in the turnover of a special class of membrane phospholipids i.e. the (poly)phosphoinositides. Evidence was obtained to suggest that the degree of phosphorylation of the B-50 protein determines the conversion of diphosphoinositol to triphosphoinositol. A model which links the protein phosphorylation to lipid phosphorylation and which points to a functional role for peptides in the regulation of the permeability of brain membranes for calcium ions will be discussed. As the structure-activity relationship for the peptide effects on grooming behavior closely resembles that on phosphorylation, it is assumed that this neurochemical event may indeed be of relevance to the biological activity of the peptide. As the ion permeability may be altered by the peptide it can be suggested that this may lead to modulation of transynaptic information processing in the brain.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006120:Grooming; D006801:Humans; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats
D009419:Nerve Tissue Proteins; D010455:Peptides; D010743:Phospholipids; D010750:Phosphoproteins; D000324:Adrenocorticotropic Hormone