ACTH and adrenal aerobic glycolysis. II: Effects of aminoterminal peptide fragments on lactic acid and steroid production by mouse adrenocortical cells.
The effects of shortening the ACTH molecule from either end of the peptide chain on adrenal glycolysis and steroidogenesis were examined in mouse adrenal cell suspensions. Shortening the (1-24) sequence to (1-17), (1-16) and (1-14), thereby interfering with the basic tetrapeptide (15-18) assigned to the address message, progressively reduced both glycolytic and steroidogenic potencies by four, six and ten orders of magnitude respectively, without impairing the capacity for maximal excitation. The glycolytic potency of the (1-18) sequence, which was amidated at the C-terminal, equalled that of ACTH (1-24), but the steroidogenic potency was reduced by an order of magnitude. The (1-13) sequence of alpha-MSH, which contains substitutions at both terminals, had glycolytic and steroidogenic potencies intermediate between those of ACTH(1-16) and ACTH(1-17). Deletion of Ser1,Tyr2 from ACTH(1-18)-NH2 reduced both potencies by an order of magnitude. ACTH(11-24) and (7-38) were inactive or inhibitory. The capacity for excitation was further examined by comparing responses to peptide fragments (1-4), (1-10), (1-13), (4-10), (4-11), (5-10), (5-14), (7-13) and (11-24) at a concentration of 1 mmol/l. All fragments, excepting (1-4), (5-10) and (11-24) were active. The activities of fragments (5-14) and (7-13), as opposed to (5-10), suggest that the requirements for methionine in position 4 may be replaced by the (11-13) tripeptide.(ABSTRACT TRUNCATED AT 250 WORDS)
Hinson
J
J
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Birmingham
M K
MK
D000302:Adrenal Cortex / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives*; D000818:Animals; D003345:Corticosterone / Q000096:biosynthesis*; D006019:Glycolysis / Q000187:drug effects; D007773:Lactates / Q000096:biosynthesis*; D019344:Lactic Acid; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*
D007773:Lactates; D010446:Peptide Fragments; D019344:Lactic Acid; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone