Acute stress results in skin corticotropin-releasing hormone secretion, mast cell activation and vascular permeability, an effect mimicked by intradermal corticotropin-releasing hormone and inhibited by histamine-1 receptor antagonists.
BACKGROUND
Mast cells play an important role in allergic inflammation by releasing vasoactive molecules, proteases and cytokines. Corticotropin-releasing hormone (CRH) and its structural analogue urocortin (Ucn) were shown to trigger skin mast cell activation and vascular permeability. We investigated the effect of acute stress on rat skin vascular permeability and CRH secretion, as well as the effect of intradermal CRH, and that of two histamine-1 receptor antagonists, azelastine and olopatadine, on vascular permeability.


METHODS
Rats were stressed by restraint and vascular permeability was assessed by extravasation of (99)Tc-gluceptate, while mast cell activation was determined by skin rat mast cell protease-1 (RMCP-1) content. Skin CRH content was evaluated by ELISA. The effect of intradermal injection of CRH and Ucn, as well as that of two histamine-1 receptor antagonists, azelastine and olopatadine, was assessed by Evan's blue extravasation. Purified rat peritoneal mast cells (RPMCs) were also pretreated with azelastine (24 microM) or olopatadine (133 microM) for 5 min before challenge with compound 48/80 (0.5 microg/ml) for 30 min. Histamine secretion was measured fluorometrically. Intracellular Ca(2+) ions were evaluated in RPMCs loaded with calcium crimson and stimulated with compound 48/80.


RESULTS
Acute stress increased skin vascular permeability and CRH content, while it decreased RMCP-1. Intradermal injection of CRH or Ucn induced substantial Evan's blue extravasation that was inhibited by pretreatment with azelastine (24 microM) and olopatadine (133 microM). Both antihistamines also inhibited histamine release and intracellular increase of Ca(2+) ions from RPMCs stimulated by compound 48/80.


CONCLUSIONS
These results indicate that acute stress increases skin CRH that can trigger mast cell-dependent vascular permeability, effects inhibited by certain histamine-1 receptor antagonists, possibly acting to reduce intracellular Ca(2+) ion levels.
Lytinas
Michael
M
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.
Kempuraj
Duraisamy
D
Huang
Man
M
Boucher
William
W
Esposito
Pamela
P
Theoharides
Theoharis C
TC
D000208:Acute Disease; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000378:metabolism*; D003990:Dibenzoxepins / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D007271:Injections, Intradermal; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000502:physiology*; D000069605:Olopatadine Hydrochloride; D010793:Phthalazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D013312:Stress, Physiological / Q000276:immunology / Q000503:physiopathology*
D003990:Dibenzoxepins; D006634:Histamine H1 Antagonists; D010793:Phthalazines; D000069605:Olopatadine Hydrochloride; D003346:Corticotropin-Releasing Hormone; D002118:Calcium; C020976:azelastine