A neurotensin receptor antagonist inhibits acute immobilization stress-induced cardiac mast cell degranulation, a corticotropin-releasing hormone-dependent process.
Stress worsens certain disorders such as migraines or asthma, and has also been implicated in sudden myocardial arrest. It was previously shown that acute psychological stress by immobilization results in dura mast cell degranulation, an effect blocked by pretreatment with antiserum against corticotropin-releasing hormone (CRH). Moreover, CRH was recently shown to induce skin mast cell degranulation. The effect of psychological stress was investigated on rat cardiac mast cells, because their release of coronary constrictive and proinflammatory molecules contributes to myocardial ischemia and possibly arrhythmias. Immobilization of rats for 30 min induced maximal cardiac mast cell degranulation as evidenced by light and electron microscopy. This effect was inhibited by pretreatment with the "antiallergic" drug sodium cromoglycate (cromolyn), which is thought to act primarily through mast cell stabilization. Mast cell degranulation was also blocked by preincubation with antiserum against CRH and was partially inhibited by a CRH type-1 receptor selective antagonist. Sensory neuropeptides did not appear to influence this effect, but a nonpeptide neurotensin receptor antagonist blocked stress-induced cardiac mast cell degranulation. This finding supports the involvement of neuropeptide neurotensin which is present in the heart and is known to trigger mast cell degranulation. These results indicate acute stress could result in local CRH and nonpeptide neurotensin release which could contribute to myocardial pathophysiology through direct or indirect release of cardiac mast cell mediators.
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Medford, Massachusetts, USA.
X
X
Pang
N
N
Alexacos
R
R
Letourneau
D
D
Seretakis
W
W
Gao
W
W
Boucher
D E
DE
Cochrane
T C
TC
Theoharides
D000818:Animals; D002452:Cell Count; D015550:Cell Degranulation / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D006632:Histamine / Q000032:analysis; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors*; D013315:Stress, Psychological / Q000378:metabolism*; D013373:Substance P / Q000502:physiology
D018028:Receptors, Neurotensin; D013373:Substance P; D006632:Histamine; D003346:Corticotropin-Releasing Hormone