Antiinflammatory influences of alpha-MSH molecules: central neurogenic and peripheral actions.
alpha-Melanocyte-stimulating hormone (alpha-MSH1-13) and its COOH-terminal tripeptide alpha-MSH11-13 (Lys Pro Val) inhibit inflammation when administered systemically. Recent evidence indicates that alpha-MSH1-13 can likewise inhibit inflammation in the skin solely via an action within the brain. Because of the potential importance of this discovery to understanding the control of inflammation and because alpha-MSH molecules might be useful for treatment of inflammation, experiments were performed to learn more about the mechanisms of action of these peptides. In tests on inflammation induced in the mouse ear by intradermal injections of recombinant human interleukin-1 beta, alpha-MSH1-1-13 administered intracerebroventricularly effectively reduced inflammation. This effect of centrally administered alpha-MSH1-13 was inhibited by systemic injection of the nonspecific beta-adrenergic receptor blocker propranolol and by administration of a specific beta 2-adrenergic receptor antagonist; the effect was not altered by blockade of cholinergic, alpha-adrenergic, or beta 1-adrenergic receptors. In mice with inflammation induced in a hind paw and with the spinal cord transected, the antiinflammatory effect of centrally administered alpha-MSH1-13 was prevented, indicating that intact descending neuronal pathways are required for the antiinflammatory influence of the central peptide. Systemic injection of alpha-MSH1-13 in animals with spinal cord transection had a smaller and later antiinflammatory effect, which suggests that the molecule also has an action, albeit lesser, in the periphery. However, alpha-MSH11-13 injected intraperitoneally had marked antiinflammatory activity in animals with spinal cord transection.(ABSTRACT TRUNCATED AT 250 WORDS)
Macaluso
A
A
Department of Physiology, University of Texas Southwestern Medical Center at Dallas 75235-9040.
McCoy
D
D
Ceriani
G
G
Watanabe
T
T
Biltz
J
J
Catania
A
A
Lipton
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002078:Butoxamine / Q000494:pharmacology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004487:Edema / Q000517:prevention & control; D005260:Female; D007276:Injections, Intraventricular; D009074:Melanocyte-Stimulating Hormones / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000502:physiology*; D000521:alpha-MSH / Q000008:administration & dosage / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010446:Peptide Fragments; D017981:Receptors, Neurotransmitter; D002078:Butoxamine; D001262:Atenolol; D000521:alpha-MSH; C043156:MSH (11-13); D001285:Atropine; D009074:Melanocyte-Stimulating Hormones; D010646:Phentolamine