6533b85dfe1ef96bd12bea08

RESEARCH PRODUCT

Beta- and gamma-melanocortins inhibit lipopolysaccharide induced nitric oxide production in mice brain.

Liga ZvejnieceJarl E. S. WikbergOlga KirjanovaMaija DambrovaIvars KalvinshLarisa BaumaneEdgars LiepinshRuta MucenieceLiga Krigere

subject

LipopolysaccharidesMaleendocrine systemmedicine.medical_specialtyLipopolysaccharideCentral nervous systemInflammationPharmacologyBiologyNitric OxideNitric oxidechemistry.chemical_compoundMicegamma-MSHIn vivoInternal medicinebeta-MSHmedicineAnimalsMolecular BiologyNeuroinflammationMelanocortinsFeedback PhysiologicalMice Inbred ICRintegumentary systemDose-Response Relationship DrugGeneral NeuroscienceElectron Spin Resonance SpectroscopyBrainDisease Models Animalmedicine.anatomical_structureEndocrinologychemistryalpha-MSHNeurology (clinical)Melanocortinmedicine.symptomInflammation Mediatorshormones hormone substitutes and hormone antagonistsDevelopmental BiologySignal Transduction

description

The pro-opiomelanocortin-derived peptide alpha-melanocyte stimulating hormone (alpha-MSH) mediates many diverse physiological actions, including anti-inflammatory and immunomodulatory effects. However, little is known about the physiological roles of the other melanocortins, beta- and gamma-MSH. Here, we investigated the effects of melanocortin peptides in an in vivo neuroinflammation model. Six hours following intracisternal (i.c.) administration of 10 microg lipopolysaccharide (LPS) to mice a five-fold increase in the nitric oxide (NO) level was seen in the animals' brains, when detected by electron paramagnetic resonance (EPR). All tested melanocortins, alpha-, beta-, gamma1- and gamma2-MSH (0.001-10 nmol/mouse i.c.), dose dependently reduced the LPS induced increases in brain NO, with an order of effectiveness: beta-MSHor = gamma1-MSH=gamma2-MSHalpha-MSH. Our results suggest specialized functions of beta- and gamma-MSH melanocortins in inflammatory signal modulation in the brain.

10.1016/j.brainres.2003.09.039https://pubmed.ncbi.nlm.nih.gov/14644465