Antipyretic properties of centrally administered alpha-MSH fragments in the rabbit.
alpha-Melanocyte stimulating hormone (alpha-MSH 1-13) has marked antipyretic effects when administered centrally or peripherally in small doses. A C-terminal fragment, alpha-MSH (11-13), contains an antipyretic message sequence of alpha-MSH; however, the lesser potency of this fragment relative to that of the entire molecule suggests that other amino acids of the alpha-MSH sequence are essential for the full antipyretic effect. Graded doses of alpha-MSH (11-13) (Ac LysProVal NH2), alpha-MSH (10-13) (Ac GlyLysProVal NH2), and alpha-MSH (8-13) (Ac ArgTrpGlyLysProVal NH2), were injected into the cerebral ventricles of rabbits made febrile by IV administration of crude interleukin-1. All three fragments reduced fever in a dose-related manner. The (8-13) sequence was much more effective than the other two fragments, and the (10-13) portion was less effective than the (11-13) tripeptide. None of the fragments was as potent as alpha-MSH (1-13). The results confirm that an antipyretic message resides within alpha-MSH (11-13) and sequential addition of amino acids to alpha-MSH (11-13) can both enhance and reduce the potency of the fragment.
Deeter
L B
LB
Physiology Department, University of Texas Southwestern Medical Center, Dallas 75235-9040.
Martin
L W
LW
Lipton
J M
JM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology*; D007276:Injections, Intraventricular; D007375:Interleukin-1; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D012016:Reference Values; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D010446:Peptide Fragments; D000521:alpha-MSH