Urocortin (Ucn) is related to corticotropin-releasing hormone (CRH), and both are released in the brain under stress where they stimulate CRH 1 and 2 receptors (CRHR). Outside the brain, they may have proinflammatory actions through activa- tion of mast cells, which are located perivascularly close to nerve endings and degranulate in response to acute psycho- logical stress. Here, we report that a concentration of intrader- mal Ucn as low as 10 nM induced dose-dependent rat skin mast cell degranulation and increased vascular permeability. This effect appeared to be equipotent to that of calcitonin gene-related peptide and neurotensin. Ucn-induced skin vaso- dilation was inhibited by pretreatment with the mast cell stabi- lizer disodium cromoglycate (cromolyn) and was absent in the mast cell-deficient W/Wv mice. The selective nonpeptide CRH receptor 1 antagonist, antalarmin and the nonselective peptide antagonist astressin both reduced vascular permeability trig- gered by Ucn but not that by Substance P or histamine. In contrast, the peptide antagonist
