Resveratrol (Res) is a phytoalexin produced naturally by several plants, which has multi functional effects such as neuroprotection, anti-inflammatory, and anti-cancer. The present study was to evaluate a possible anti-epileptic effect of Res against kainate-induced temporal lobe epilepsy (TLE) in rat. We performed behavior monitoring, intracranial electroencepholography (IEEG) recording, histological analysis, and Western blotting to evaluate the anti-epilepsy effect of Res in kainate-induced epileptic rats. Res decreased the frequency of spontaneous seizures and inhibited the epileptiform discharges. Moreover, Res could protect neurons against kainate-induced neuronal cell death in CA1 and CA3a regions and depressed mossy fiber sprouting, which are general histological characteristics both in TLE patients and animal models. Western blot revealed that the expression level of kainate receptors (KARs) in hippocampus was reduced in Res-administrated rats compared to that in epileptic ones. These results suggest that Res is a potent anti-epilepsy agent, which protects against epileptogenesis and progression of the kainate-induced TLE animal.

Contractility of mesangial cells (MC) is tightly controlled by [G lomerular mesangial cells (MC) are located within glomerular capillary loops and contribute to the physiologic regulation of glomerular hemodynamics (1). Altered responsiveness of MC to hormones is one of the major causes that lead to various renal diseases. Ca 2ϩ influx across the plasma membrane is a major component of MC responses to vasoconstrictors (1). Several types of Ca 2ϩ -conductive channels in the plasma membrane are involved in the physiologic processes. These channels include voltage-operated Ca 2ϩ channel (VOCC), receptor-operated channel (ROC), and recently found store-operated channel (SOC) (1,2). In contrast to the widely known VOCC, the molecular identity, physiologic significance, and regulatory mechanism of ROC and SOC in the glomerular contractile cells remain unknown.Recently, the channel proteins from a new family, canonical transient receptor potential (TRPC), were found in a variety of cells (3). TRPC family includes seven related members, designated as TRPC1 through 7 (3). Pharmacologic and electrophysiologic studies in conjunction with molecular biologic tools and Ca 2ϩ imagings have demonstrated that TRPC channel activity is tightly linked to the signaling cascade of G protein-coupled receptor or receptor tyrosine kinase (4,5), supporting the current hypothesis that TRPC proteins are potential candidates for ROC and SOC. TRPC proteins have been identified in glomeruli and glomerular MC (6 -8). Our previous work also demonstrated that human MC selectively express TRPC1,3,4, and 6 (9). However, the function, regulation, and physiologic relevance of these glomerular TRPC are unexplored at large extent. In this study, we focused on TRPC1 and investigated its contribution to mesangial contraction in vitro and in vivo. Our results indicate that TRPC1 is an important component mediating contractile responses of MC. The TRPC1-involved mesangial contraction is attributed to TRPC1-associated Ca 2ϩ influx. Materials and Methods AnimalsTwo-to 3-mo-old male Sprague-Dawley rats were used in this study. All rats were purchased from Harlan (Indianapolis, IN). Care and use of all animals in this study were in strict agreement with the guidelines set forth by the University of North Texas Health Science Center. Measurement of GFR and Renal Blood FlowGFR and renal blood flow (RBF) were estimated by measurement of inulin and para-aminohippurate (PAH) plasma clearances as described

AIM:To study the origin of calcium necessary for agonist-induced contraction of the distal colon in rats. METHODS:The change in intracel lular calcium concentration ([Ca 2+ ]i) evoked by elevating external Ca 2+ was detected by fura 2/AM fluorescence. Contractile activity was measured with a force displacement transducer. Tension was continuously monitored and recorded using a Powerlab 4/25T data acquisition system with an ML110 bridge bioelectric physiographic amplifier. RESULTS:Store depletion induced Ca 2+ influx had an effect on [Ca 2+ ]i. In nominally Ca 2+ -free medium, the sarco-endoplasmic reticulum Ca 2+ -ATPase inhibitor thapsigargin (1 µmol/L) increased [Ca 2+ ]i from 68 to 241 nmol/L, and to 458 (P < 0.01) and 1006 nmol/L (P < 0.01), respectively, when 1.5 mmol/L and 3.0 mmol/L extracellular Ca 2+ was reintroduced. Furthermore, the change in [Ca 2+ ]i was observed with verapamil (5 µmol/L), La 3+ (1 mmol/L) or KCl (40 mmol/L) in the bathing solution. These channels were sensitive to La 3+ (P < 0.01), insensitive to verapamil, and voltage independent. In isolated distal colons we found that in normal Krebs solution, contraction induced by acetylcholine (ACh) was partially inhibited by verapamil, and the inhibitory rate was 41% (P < 0.05). On the other hand, in Ca 2+ -free Krebs solution, ACh induced transient contraction due to Ca 2+ release from the intracellular stores. The transient contraction lasted until the Ca 2+ store was depleted. Restoration of extracellular Ca 2+ in the presence of atropine produced contraction, mainly due to Ca 2+ influx. Such contraction was not inhibited by verapamil, but was decreased by La 3+ (50 µmol/L) from 0.96 to 0.72 g (P < 0.01). CONCLUSION:The predominant source of activator C a 2 + f o r t h e c o n t ra c t i l e r e s p o n s e t o a g o n i s t i s extracellular Ca 2+ , and intracellular Ca 2+ has little role to play in mediating excitation-contraction coupling by agonists in rat distal colon smooth muscle in vitro . The influx of extracellular Ca 2+ is mainly mediated through voltage-, receptor-and store-operated Ca 2+ channels, which can be used as an alternative to develop new drugs targeted on the dysfunction of digestive tract motility.