European journal of pharmacology
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Comparative Study
Inhibition of interleukin-1beta reduces mouse lung inflammation induced by exposure to cigarette smoke.
We examined nuclear factor kappaB activation, release of inflammatory mediators and cellular infiltration in acute cigarette smoke inflammation models. One hour after exposure to one puff of cigarette smoke, alveolar macrophages from bronchoalveolar lavage (BAL) fluid of C57BL/6J mice showed an increased activity of nuclear factor kappaB-DNA binding but similar numbers as compared to that of BAL fluid from mice exposed to ambient air. Exposure to 1 cigarette/day for 1, 4 or 7 days led to an increase in interleukin-1beta and monocyte chemoattractant protein-1 levels and to a progressive influx of nuclear factor kappaB-activated alveolar macrophages into the BAL fluid and lung tissue. ⋯ Tumor necrosis factor-alpha levels and subsequent neutrophil influx were only detected after exposure to 4 or 8 cigarettes/day for 7 days. Treatment of mice with an antibody anti-interleukin-1beta during cigarette smoke exposure for 7 days significantly reduced both interleukin-1beta levels and alveolar macrophage influx. These data show that a single exposure to cigarette smoke rapidly activates alveolar macrophages, inducing the production of interleukin-1beta, which may play an important role in triggering chronic cigarette smoke-mediated lung inflammation.
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Comparative Study
Upregulation of Rho-kinase (ROCK-2) expression and enhanced contraction to endothelin-1 in the mesenteric artery from lipopolysaccharide-treated rats.
Effects of bacterial lipopolysaccharide (Escherichia coli serotype, 055:B5, 20 mg kg(-1), i.p., for 6 h) and a Rho-kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate, Y-27632 (10(-9)-10(-5) M) were investigated on the contractile responses of the rat mesenteric artery to phenylephrine (10(-9)-3 x 10(-5) M), angiotensin-2 (10(-10)-10(-6) M) and endothelin-1 (10(-10)-10(-7) M). Moreover, alteration in the level of Rho-kinase (ROCK-2) expression was examined in the superior mesenteric artery obtained from saline- and lipopolysaccharide-treated rats by Western blotting. Endotoxemic rat mesenteric rings exhibited no different contractions to phenylephrine and angiotensin-2 but augmented contractile activity to endothelin-1. ⋯ Western blot analysis revealed that Rho-kinase was upregulated significantly in the mesenteric artery obtained from the rats treated with LPS for 6 h. In addition, serum NO2-/NO3- level, which was detected by Griess method, was 10.0+/-1.4 microM in endotoxemic rats; however, it was 6.6+/-0.5 microM in control (P<0.05). Taken together, these results show that the expression of the contractile protein Rho-kinase could be upregulated in endotoxemic mesenteric artery and this upregulation may be coincided with an enhanced contraction to endothelin-1 but not phenylephrine and angiotensin-2.
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Somatostatin released from capsaicin-sensitive sensory nerves exerts systemic anti-inflammatory and antinociceptive actions. TT-232 is a stable, peripherally acting heptapeptide (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-Thr-NH2) somatostatin analogue with highest binding affinity for somatostatin sst4 receptors. It has been shown to inhibit acute and chronic inflammatory responses and sensory neuropeptide release from capsaicin-sensitive nociceptors. ⋯ Five weeks after streptozotocin administration (50 mg/kg i.v.) the diabetes-induced decrease in the mechanonociceptive threshold was inhibited by 10-100 microg/kg i.p. TT-232. These findings show that TT-232 potently inhibits acute chemical somatic/visceral and thermal nociception and diminishes chronic mechanical allodynia associated with diabetic neuropathy, thereby it could open new perspectives in the treatment of various pain syndromes.
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Comparative Study
Antitussive effect of NS-398, a selective cyclooxygenase-2 inhibitor, in guinea pigs.
Several reports have demonstrated that the number of capsaicin-induced coughs is increased in the presence of prostaglandins in the airway. Moreover, it has been reported that the expression of cyclooxygenase-2, which converts arachidonic acid to prostaglandins, was found in cultured human airway epithelial cells in the absence of inflammatory cytokine stimulation. Thus, it is possible that cyclooxygenase-2 inhibitor may produce an antitussive effect. ⋯ Furthermore, it is possible that the antitussive action of NS-398 does not depend on centrally acting mechanisms, since 5-HT receptors play an important role in the cough-depressant activities of centrally acting antitussive drugs. NS-398 may exert peripheral antitussive effects by inhibiting the release of substance P from capsaicin-sensitive afferent C-fibers in the airways. These results suggest that cyclooxygenase-2 inhibitors may have a therapeutic benefit in reducing coughs.
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Comparative Study
The involvement of alpha 2A-adrenoceptors in morphine analgesia, tolerance and withdrawal in mice.
Alpha(2)-adrenoceptor agonists potentiate opioid analgesia and alleviate opioid withdrawal. The effects of two alpha(2)-adrenoceptor agonists, clonidine (2 mg/kg) and dexmedetomidine (20 and 100 microg/kg), and the alpha(1)-adrenoceptor antagonist prazosin (0.5 mg/kg) were tested on morphine analgesia, tolerance, and withdrawal in wild-type and alpha(2A)-adrenoceptor knock-out (KO) mice. Analgesia and tolerance were assessed with the tail-flick test. ⋯ Alpha(2A)-Adrenoceptor KO mice exhibited 70% fewer naloxone-precipitated jumps than wild-type mice; weight loss was similar in both genotypes. The alpha(2)-adrenoceptor agonists reduced opioid withdrawal signs only in wild-type mice. We conclude that alpha(2A)-adrenoceptors are not directly involved in morphine analgesia and tolerance, and not critical for potentiation of morphine analgesia by prazosin, but that alpha(2A)-adrenoceptors modulate the expression of opioid withdrawal signs in mice.