The Melanocortin Receptor System: An Anti‐Inflammatory Therapeutic Target For Stroke

A disproportionate inflammatory response has been shown to play a major deleterious role in the pathogenesis of a wide variety of disorders and is increasingly being acknowledged as a major pathological factor in stroke. Therefore, targeting the inflammatory response in stroke may dramatically increase the time window for therapeutic intervention, and improve functional outcome in this debilitating disease. The melanocortin receptors are a family of G‐protein coupled rhodopsin‐like receptors with key regulatory functions in a wide variety of cellular processes. These receptors are increasingly being recognised as exciting pharmacological targets for a number of different pathologies. Here we determined their therapeutic value in stroke. Cerebral leukocyte endothelial interactions were assessed post stroke (bilateral common carotid artery occlusion model) using intravital microscopy. Both leukocyte rolling and adherence were increased in mice subjected to stroke vs. sham mice. Prophylactic treatment with the pan receptor agonist α‐MSH (10μg i.p) significantly reduced rolling and adhesion as did the MC3 selective agonist, Dtrp8‐γ‐MSH (10μg i.p). These novel results suggest that although selective activation of the MC3 leads to an attenuation of inflammation following stroke, multiple melanocortin receptor subtypes may be involved, acting in a synergistic manner.