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Evidence that melanocortin 4 receptor mediates hemorrhagic shock reversal caused by melanocortin peptides.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 1999 Dec; Vol. 291 (3), pp. 1023-7. - Publication Year :
- 1999
-
Abstract
- Melanocortin peptides are known to be extremely potent in causing the sustained reversal of different shock conditions, both in experimental animals and humans; the mechanism of action includes an essential brain loop. Three melanocortin receptor subtypes are expressed in brain tissue: MC(3), MC(4,) and MC(5) receptors. In a volume-controlled model of hemorrhagic shock in anesthetized rats, invariably causing the death of control animals within 30 min after saline injection, the i.v. bolus administration of the adrenocorticotropin fragment 1-24 (agonist at MC(4) and MC(5) receptors) at a dose of 160 microg/kg i.v. (54 nmol/kg) produced an almost complete and sustained restoration of cardiovascular and respiratory functions. An equimolar dose of gamma(1)-melanocyte stimulating hormone (selective agonist at MC(3) receptors) was completely ineffective. The selective antagonist at MC(4) receptors, HS014, although having no influence on cardiovascular and respiratory functions per se, dose-dependently prevented the antishock activity of adrenocorticotropin fragment 1-24, with the effect being complete either at the i.v. dose of 200 microg/kg or at the i.c.v. dose of 5 microg/rat (17-20 microg/kg). We concluded that the effect of melanocortin peptides in hemorrhagic shock is mediated by the MC(4) receptors in the brain.
- Subjects :
- Animals
Blood Pressure drug effects
Blood Pressure physiology
Blood Volume physiology
Brain Chemistry drug effects
Cosyntropin pharmacology
Female
Heart Rate drug effects
Heart Rate physiology
Male
Peptides therapeutic use
Rats
Rats, Wistar
Receptor, Melanocortin, Type 4
Receptors, Corticotropin drug effects
Respiratory Mechanics drug effects
Shock, Hemorrhagic physiopathology
Melanocyte-Stimulating Hormones therapeutic use
Receptors, Corticotropin physiology
Shock, Hemorrhagic drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3565
- Volume :
- 291
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 10565820