Modulation of brain polyphosphoinositide metabolism by ACTH and beta-endorphin: structure-activity studies.
This study describes effects of ACTH1-24 and beta-endorphin on brain polyphosphoinositide metabolism in vitro. The interconversion of these polyanionic phospholipids was studied by incubation of a lysed synaptosomal fraction with [gamma-32P]ATP. Of the membrane phospholipids only PA, DPI and TPI became labeled. The reference peptide ACTH1-24 stimulated the formation of TPI and inhibited the production of PA. For effects on TPI formation both the sequences ACTH5-7 and ACTH10-16 were needed. Effects on PA formation required the sequences ACTH7-10 and ACTH10-16. The basic amino acids in ACTH10-16 seemed to be of crucial importance for the peptide effects. A stimulatory effect on DPI was visible when ACTH was shortened from the N-terminus, and the essential information was in ACTH7-10. beta-endorphin inhibited PA formation and this effect was abolished by C-terminal shortening to gamma-endorphin. Other fragments of the C-terminus of beta-LPH, including the enkephalins, were ineffective. It is concluded that the structure-activity relationship on TPI/PA formation correlates with a similar relationship obtained on excessive grooming behavior in vivo. A possible correlation between the effects on polyPI metabolism and opiate-like effects, and effects on extinction of active avoidance behavior in vivo is discussed.
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004723:Endorphins / Q000494:pharmacology*; D008297:Male; D009928:Organ Specificity; D010716:Phosphatidylinositols / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D001615:beta-Endorphin
D004723:Endorphins; D010716:Phosphatidylinositols; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D011494:Protein Kinases