Ergopeptine-sensitive calcium-dependent protein phosphorylation system in the brain.
We studied a protein phosphorylation system that is regulated by the dopamine-mimetic ergot bromocriptine. Bromocriptine was found to inhibit selectively the endogenous phosphorylation of a threonine residue(s) in 50,000- and 60,000-dalton proteins in a synaptosome fraction. The bromocriptine-sensitive phosphorylation is stimulated by calcium and by calmodulin, and occurs predominantly in the brain. The inhibitory effect of bromocriptine was not mimicked by 3,4-dihydroxyphenylethylamine or by any of the neurotransmitters and related agents tested, but was mimicked, although less effectively, by other ergots that contain peptide moieties. In the hippocampus, the brain region with the highest content of the 50,000- and 60,000-dalton proteins, the ergopeptine-sensitive protein phosphorylation appears to be localized to interneurons or cell bodies whose axons synapse outside the hippocampus. The results raise the possibility that some of the bromocriptine- and ergopeptine-induced pharmacological effects in the CNS may be mediated by the inhibition of the calcium/calmodulin-dependent phosphorylation of these specific proteins.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001971:Bromocriptine / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D006168:Guinea Pigs; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000032:analysis; D010748:Phosphopeptides / Q000032:analysis; D010750:Phosphoproteins / Q000302:isolation & purification; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism*
D000596:Amino Acids; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D010748:Phosphopeptides; D010750:Phosphoproteins; D001971:Bromocriptine; D002118:Calcium