Mast cells play a key role in modulation of stress-induced cutaneous inflammation. In this study we investigate the impact of repeated exposure to stress on mast cell degranulation, in both hairy and glabrous skin. Adult male Wistar rats were randomly divided into four groups: Stress 1 day (n = 8), Stress 10 days (n = 7), Stress 21 days (n = 6), and Control (n = 8). Rats in the stress groups were subjected to 2 h/day restraint stress. Subsequently, glabrous and hairy skin samples from animals of all groups were collected to assess mast cell degranulation by histochemistry and transmission electron microscopy. The impact of stress on mast cell degranulation was different depending on the type of skin and duration of stress exposure. Short-term stress exposure induced an amplification of mast cell degranulation in hairy skin that was maintained after prolonged exposure to stress. In glabrous skin, even though acute stress exposure had a profound stimulating effect on mast cell degranulation, it diminished progressively with long-term exposure to stress. The results of our study reinforce the view that mast cells are active players in modulating skin responses to stress and contribute to further understanding of pathophysiological mechanisms involved in stress-induced initiation or exacerbation of cutaneous inflammatory processes.

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1 Adenosine 5 0 -triphosphate (ATP) is known to augment cardiac contractile activity and cause an increase in intracellular Ca 2 þ concentration ([Ca 2 þ ] i ) in isolated cardiomyocytes. However, no information regarding the ATP-mediated signal transduction in the myocardium in congestive heart failure (CHF) is available. 2 CHF due to myocardial infarction (MI) in rats was induced by the occlusion of the left coronary artery for 8 weeks. The positive inotropy due to ATP was depressed in failing hearts. Treatment of 3 weeks infarcted animals with imidapril (1 mg kg À1 day À1 ) for a period of 5 weeks improved the left ventricle function and decreased the attenuation of inotropic response to ATP. 3 ATP-induced increase in [Ca 2 þ ] i was significantly depressed in cardiomyocytes isolated from the failing heart and this change was partially attenuated by imidapril treatment. However, the binding characteristics of 35 S-labeled adenosine 5 0 -(g-thio) triphosphate in sarcolemma isolated from the failing heart remained unaltered. 4 ATP-induced increase in [Ca 2 þ ] i was depressed by verapamil and cibacron blue in both control and failing heart cardiomyocytes; however, the ATP response in the failing hearts, unlike the control preparations, was not decreased by ryanodine. This insensitivity to ryanodine was attenuated by imidapril treatment. 5 Treatment of infarcted rats with enalapril and losartan produced effects similar to imidapril. 6 These findings indicate that the positive inotropic response to ATP and ATP-induced increase in [Ca 2 þ ] i in cardiomyocytes are impaired in heart failure. Furthermore, blockade of renin angiotensin system prevented the impairment of the ATP-mediated inotropic and [Ca 2 þ ] i responses in the failing heart.

We previously demonstrated that cardiac sarcolemmal membranes bind [35S]ATP gamma S at both low and high affinity binding sites. In this study we examined the effects of some P2-purinoceptor antagonists as well as of two oxidants (H2O2 and HOCl) on the high affinity ATP-binding sites under in vitro conditions. It was found that putative P2-purinoceptor antagonists such as Cibacron blue, suramin, and 4,4'-diisothiocyanatostilbene 2-2 acid markedly inhibited specific ATP-binding with sarcolemmal membrane. H2O2 produced a biphasic effect (first increase and then decrease) on the specific ATP-binding with cardiac sarcolemma in a time- and concentration-dependent manner; these effects were prevented by catalase. On the other hand, HOCl markedly inhibited ATP-binding; this inhibition was prevented by l-methionine. These results suggest that the high affinity ATP-binding sites in cardiac sarcolemma may represent the P2-purinoceptors, which are susceptible to modification by oxidative stress under pathophysiological conditions including myocardial ischemia-reperfusion injury.