Does the neurotropic action of adrenocorticotrophic hormone involve a lipolytic step?
The stimulatory effect of adrenocorticotrophic hormone (ACTH)-related synthetic peptides on the hydrolysis of emulsified trioleoylglycerol by a rat brain lipase was studied. The ACTH effect was related to the net positive charge associated with the basic amino acid residues at position 15-18 in the ACTH sequence, as well as to the presence of the NH2-terminal amino acid residues at position 1-2. The ACTH effect on lipolysis was markedly reduced when lipids were partially removed from the enzyme preparation by extraction with chloroform/acetone. Full restoration of the stimulatory effect was obtained upon addition of phosphatidylcholine (2 mg/ml) to the lipolytic medium. Striking similarities between the structure-activity pattern for the stimulatory effect of ACTH on brain lipase and that described for the receptor-mediated actions of ACTH on adrenal and fat cells suggest that the ACTH effect might involve recognition of a binding site associated with the brain enzyme. Complete log concentration response curves obtained with four ACTH analogs may also be regarded as simulating hormone-receptor interaction. These findings are discussed in relation to the possibility that ACTH may have a neurohormonal role via lipase-catalyzed changes in the lipid matrix of membranes.
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008049:Lipase / Q000378:metabolism*; D008053:Lipid Mobilization / Q000187:drug effects*; D010713:Phosphatidylcholines / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D010713:Phosphatidylcholines; D000324:Adrenocorticotropic Hormone; D008049:Lipase