Naunyn-Schmiedeberg's archives of pharmacology
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Naunyn Schmiedebergs Arch. Pharmacol. · Oct 2009
The peripheral administration of a nitric oxide donor potentiates the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice.
Several works reveal that nitric oxide could enhance the peripheral antinociception induced by opioids during acute inflammation. Nonetheless, the role of nitric oxide in the local antinociceptive effects of delta-opioid receptor (DOR) agonists during chronic peripheral inflammation is not known. The aim of this study is to evaluate whether nitric oxide would enhance the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice. ⋯ Moreover, the co-administration of NOC-18 with DPDPE significantly increased the antinociceptive effects produced by DPDPE from 1 to 10 days of CFA-induced inflammatory pain (P < 0.05). These effects were completely blocked by naltrindole and naloxone methiodide. Our results demonstrate that nitric oxide might enhance the local antinociceptive effects of a DOR agonist during chronic inflammatory pain by interaction with peripheral DOR, representing a useful strategy for an efficient antinociceptive treatment of peripheral inflammatory pain.
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Naunyn Schmiedebergs Arch. Pharmacol. · Sep 2009
ReviewCoupling factor 6 as a novel vasoactive and proatherogenic peptide in vascular endothelial cells.
Coupling factor 6 (CF6) is composed of 76 amino acids and is present in the peripheral stalk of mitochondrial ATP synthase. The generation of CF6 is positively regulated by tumor necrosis factor alpha and shear stress via nuclear factor kappaB, and by high glucose via protein kinase C and p38 mitogen-activated protein kinase. CF6 is released outside of the cells from vascular endothelial cells, and binds to the beta-subunit of the plasma membrane-bound ATP synthase in vascular endothelial cells and leads to intracellular acidosis. ⋯ CF6 induces the gene and protein expression of proatherogenic molecules such as endothelin 2, urokinase type plasminogen activator receptor, estrogen receptor beta, a soluble short form of vascular endothelial growth factor receptor-1, and lectin-like oxidized low-density lipoprotein receptor-1. The plasma level of CF6 is elevated in patients with essential hypertension, diabetes mellitus, end-stage renal disease, acute myocardial infarction, and coronary heart disease. It is likely that CF6 contributes to the pathogenesis of cardiovascular diseases, but further intensive investigation is needed.
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Naunyn Schmiedebergs Arch. Pharmacol. · Aug 2009
Effects of a single postnatal methamphetamine administration on NMDA-induced seizures are sex- and prenatal exposure-specific.
The aim of our study was to reveal whether acute methamphetamine (MA) administration changes the sensitivity to seizures induced by N-methyl-D-aspartate (NMDA) in prenatally MA-exposed adult rats. Adult rats with respect to sex and female estrous cycle (prenatally MA-exposed, prenatally saline-exposed, and controls) were divided into groups with acute MA (1 mg/kg) or without acute drug administration (saline injection). Intraperitoneal administration of 250 mg/kg of NMDA was used as a seizure model. ⋯ In addition, males displayed decreased susceptibility to NMDA-induced seizures relative to females regardless of their estrous cycle. Our study suggests that acute MA exposure changes susceptibility to NMDA-induced seizures in respect of prenatal exposure and sex. However, it seems that the effect of prenatal exposure is not induced by the drug per se but rather by the repeated injection exposure that causes prenatal stress.
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Naunyn Schmiedebergs Arch. Pharmacol. · Aug 2009
Comparative StudyTopical antiseptics for the treatment of sore throat block voltage-gated neuronal sodium channels in a local anaesthetic-like manner.
Lozenges for the treatment of sore throat provide relief of discomfort in cases of oral inflammation. This effect has not been fully explained so far. Here, we have examined the proposition that key components of pharmaceutical preparations for the treatment of sore throat which are routinely regarded antiseptics might have sodium channel-blocking, i.e. local anaesthetic-like effects. ⋯ Estimates for the inactivated state affinity were 1.88 and 35 microM for hexylresorcinol and amylmetacresol, respectively. Hexylresorcinol and amylmetacresol are 10-20 fold more potent than the local anaesthetic lidocaine in blocking sodium inward current. Both drugs show an increased effect at depolarised membrane potentials or in conditions of high-frequency discharges.
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Naunyn Schmiedebergs Arch. Pharmacol. · Jul 2009
Comparative StudyThe anti-arrhythmic peptide AAP10 remodels Cx43 and Cx40 expression and function.
The anti-arrhythmic peptide AAP10 has previously been shown to acutely upregulate electrical cell-to-cell coupling mediated via connexin 43 gap junctions. In the present work, we have further examined the connexin (Cx) specificity and mechanism of action of this peptide in HeLa cells expressing Cx43, Cx40 or Cx26. The ability of cells to transfer the small fluorescent dyes Alexa 488 (MW 570) or Alexa 594 (MW 759), as markers for metabolic coupling mediated via gap junctions, before and after exposure to AAP10 and/or the protein kinase C inhibitor chelerythrine for 5 h was determined by microinjection analysis. ⋯ By contrast, AAP10 had no effect on the ability of Cx26 gap junctions to transfer the dyes or on the level of Cx26 expression. We propose that AAP10 is a versatile peptide that remodels metabolic coupling via Cx43 and to a lesser extent Cx40 gap junction channels via an initial protein-kinase-C-dependent pathway modifying local responses at the plasma membrane. This is followed by enhanced Cx43 or Cx40 protein expression.