Prolonged treatment with isoproterenol causes a loss of myocardial Gsalpha mRNA expression.

We investigated the influence of chronic beta-adrenergic stimulation on Gsalpha protein gene expression and beta-adrenoceptor responsiveness in rat ventricular myocardium. The rats received twice-daily injections of 4 mg/kg isoproterenol (ISO) alone or with 8 mg/kg propranolol (PROP) for 4 days. In ventricular myocardium, Gsalpha mRNA expression decreased by 27% after ISO treatment.

Bilobalide prevents reduction of gamma-aminobutyric acid levels and glutamic acid decarboxylase activity induced by 4-O-methylpyridoxine in mouse hippocampus.

We previously reported that bilobalide, a constituent of Ginkgo biloba L. leaves, protected mice against convulsions induced by 4-O-methylpyridoxine (MPN). To elucidate the mechanism of the anticonvulsant activity of bilobalide, this study examined the effect of bilobalide on MPN-induced changes in the levels of gamma-aminobutyric acid (GABA) and glutamate, and in the activity of glutamic acid decarboxylase (GAD) in the hippocampus, cerebral cortex and striatum of the mouse.

Preeclamptic serum enhances endothelin-converting enzyme expression in cultured endothelial cells.

Increased vascular sensitivity to vasoconstrictors, such as angiotensin II and epinephrine, is observed in preeclampsia (PE). Recently, it was suggested that abnormal endothelial function might contribute to the pathophysiologic changes in PE. We investigated vasoconstrictor (angiotensin II and epinephrine)-induced endothelin-1 (ET-1) release from human umbilical vein endothelial cells incubated with sera from women with PE compared with normotensive pregnant and nonpregnant women.

Modulation of phospholipase C pathway in rat cerebral cortex during aging.

The regulation of the alpha(1)-adrenoceptor-G protein-phospholipase C (PLC) cascade was investigated in rat cerebral cortex at adult (6-month-old) and senescent (24-month-old). Norepinephrine (NE)-stimulated inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] production was enhanced 30% during aging. Moreover, maximal NE (50 microM) stimulation was much more effective in stimulating G protein low-K(m) GTPase in cortical membranes from old than adult rats.

The relationship between serum nitrate and endothelin-1 concentrations in preeclampsia.

Recently it was suggested that abnormal endothelial function may contribute to the pathophysiological changes observed in preeclampsia (PE). Both nitric oxide (NO) and endothelin-1 (ET-1) are vasoactive substances produced by endothelial cells. NO is a vasodilator and has been believed to be decreased in PE.

Effects of bilobalide, a sesquiterpene in Ginkgo biloba leaves, on population spikes in rat hippocampal slices.

The effects of bilobalide, a sesquiterpene isolated from the leaves of Ginkgo biloba L., were investigated in a rat hippocampal slice preparation. Bilobalide (10-500 microM) significantly increased the amplitude of population spikes evoked by electrical stimulation of Schaffer collateral/commissural fibers in a concentration-dependent manner.

Propofol-induced depression of cultured rat ventricular myocytes is related to the M2-acetylcholine receptor-NO-cGMP signaling pathway.

Background: It is well-known that propofol sometimes causes bradycardia or asystole during anesthesia; however, the direct effect of propofol on the myocardium remains unclear. Previous reports showed the contribution of muscarinic acetylcholine receptors to propofol-induced bradycardia. Conversely, it was suggested recently that nitric oxide (NO) plays an important role in mediating the effect of vagal stimulation in the autonomic regulation of the heart.

Capacitative Ca2+ entry involves Ca2+ influx factor in rat glioma C6 cells.

Capacitative Ca2+ entry exists in rat glioma C6 cells; however, how the information of depletion of Ca2+ in intracellular stores transmits to the plasma membrane is unknown. In the present study, we examined whether Ca2+ influx factor (CIF) causes capacitative Ca2+ entry in C6 cells. CIF was extracted from non-treated (Non-CIF), bombesin-treated (BBS-CIF) and thapsigargin-treated (TG-CIF) C6 cells by a reverse-phase silica cartridge.

Effect of chronic ethanol treatment of Ca2+-inhibited adenylyl cyclase in mouse striatum.

In the present study, to investigate the possibility that chronic ethanol treatment might alter Ca2+-inhibited type 5 adenylyl cyclase (AC) activity, we examined the effect of chronic ethanol treatment on striatal dopaminergic signal transduction, especially the AC system, in mice. We fed male C57BL/6 mice for 7 days with a 5% ethanol-containing or control liquid diet. Basal and forskolin-stimulated AC activities were reduced in striatal membranes of ethanol-treated mice.

Effects of bilobalide on gamma-aminobutyric acid levels and glutamic acid decarboxylase in mouse brain.

We have previously demonstrated that bilobalide, a constituent of the Ginkgo biloba extract, possesses anticonvulsant activity, and suggested that the mechanism of its anticonvulsant action involves modulation of y-aminobutyric acid (GABA)-related neuronal transmission. This study examined the effects of bilobalide on the level of GABA and glutamate, the activity and the amount of glutamic acid decarboxylase (EC 4.1.

Role of nitric oxide production in carbachol-induced negative chronotropy in cultured rat ventricular myocytes.

It has been reported that nitric oxide (NO) plays a physiological role in mediating the effect of vagal stimulation in the autonomic regulation of the heart. In this study, the changes in NO production induced by carbachol were investigated by measuring the NO metabolites, nitrite (NO2-) and nitrate (NO3-), with a high-performance liquid chromatography-Griess reaction system, and the carbachol-induced chronotropic response was simultaneously investigated. Cultured rat ventricular myocytes exhibited a dose-dependent negative chronotropic response and NO metabolite production in response to carbachol.

The direct effect of halothane on myocardial contraction in rat myocytes with poorly developed gap junctional intercellular communication.

Background: The gap junction channel plays an important role in synchronous beating in the heart, and the reduction in the amount of gap junctional intercellular communication (GJIC) is thought to be the main arrhythmogenic factor in diseased heart. However, the effect of halothane on myocardial contraction in heart tissue with less GJIC is not well known. The purpose of the present study is to examine the direct effect of halothane on myocardium with poorly expressed GJIC.

Comparative myocardial depression of sevoflurane, isoflurane, and halothane in cultured neonatal rat ventricular myocytes.

Unlabelled: In this study, we compared the direct myocardial depressant effects of sevoflurane, isoflurane, and halothane and determined whether an L-type Ca2+ channel agonist, Bay K 8644, could attenuate the myocardial depression induced by these anesthetics in cultured neonatal rat ventricular myocytes. Ventricular myocytes were obtained from neonatal rats by enzymatic digestion with collagenase and then cultured for 6-7 days. The myocytes were stabilized in serum-free medium, and the spontaneous beating rate and contractile amplitude were measured by using a fiberoptic sensor.

Role of nitric oxide production through M2-cholinergic receptors in cultured rat ventricular myocytes.

We previously reported that carbachol (CCh) caused the enhancement of NO production coinciding with negative chronotropy in cultured rat ventricular myocytes. In this study, we examined which subtype of muscarinic cholinergic receptor mediated these effects of CCh by measuring the NOx production with an HPLC-Griess reaction system and monitoring the beating with a Fotonic Sensor. The enhancement of NO production and negative chronotropy by 10(-4) M CCh stimulation were significantly inhibited by 10(-6) M atropine, 10(-6) M methoctramine, 3 x 10(-4) M L-NMMA, and 10(-5) M methylene blue.

Ruthenium red inhibits cytosolic Ca2+ oscillations induced by vasopressin in primary cultured hepatocytes.

The effects of ruthenium red were investigated on the vasopressin (Vp)-induced Ca2+ response in single, primary cultured rat hepatocytes loaded with fura-2. Low concentrations of Vp (1 nM) evoked a sustained train of baseline spike Ca2+ oscillations, with a latency to first peak of 170 s and a frequency of 0.37 min(-1).

Relation between spontaneous contraction and sarcoplasmic reticulum function in cultured neonatal rat cardiac myocytes.

The relation between spontaneous contraction, Ca2+ oscillations, and sarcoplasmic reticulum (SR) function was studied in cultured neonatal rat cardiac myocytes. Spontaneous contraction and Ca2+ oscillations were irregular at day 2 of culture but became regular at day 6 of culture in neonatal rat cardiac myocytes. The rate of spontaneous contraction and the frequency of Ca2+ oscillations were decreased by verapamil and were abolished in the absence of extracellular Ca2+ at both day 2 and day 6 of culture.

Ca2+ channel modulation alters halothane-induced depression of ventricular myocytes.

Purpose: This study examined the direct myocardial depressant effect of halothane and determined whether an L-type Ca2+ channel agonist and antagonists altered the myocardial depression induced by halothane in cultured rat ventricular myocytes.

Methods: Ventricular myocytes were obtained from neonatal rats by enzymatic digestion with collagenase and then cultured for 6 to 7 days. The myocytes were stabilized in a serum-free medium, and the spontaneous beating rate and amplitude were measured.

Mechanism of endothelin-1 release from endothelial cells in pregnancy-induced hypertension.

We investigated the mechanism of vasoconstrictor-induced endothelin-1 (ET-1) release from human umbilical vein endothelial cells (HUVECs) in serum from women with pregnancy-induced hypertension (PIH). We obtained serum samples from seven women with PIH, seven healthy nonpregnant women (NP), and seven normal pregnant women (NPIH). ET-1 and inositol 1,4,5-trisphosphate (IP3) were assayed by ET-1 ELISA and an IP3 3H assay system, respectively.

Inhibitory effects of tyrosine kinase inhibitors on capacitative Ca2+ entry in rat glioma C6 cells.

The effects of genistein and erbstatin analogue, inhibitors of tyrosine kinase, on Ca2+ mobilization evoked by thapsigargin (TG) were examined in rat glioma C6 cells. Genistein and erbstatin analogue inhibited the Ca2+ release from intracellular pools as well as Ca2+ entry from extracellular medium evoked by TG in a dose-dependent manner. However, they did not affect a Ca2+ entry due to leakage of Ca2+ from extracellular medium into cells.

Alteration in Ca2+/calmodulin-sensitive adenylyl cyclase activity in the hippocampus of stroke-prone spontaneously hypertensive rats.

This study examined the function of adenylyl cyclase (AC) activity in the hippocampus and cerebral cortex of the stroke-prone spontaneously hypertensive rat (SHRSP). Male SHRSP (8-week-old and 25-week-old) were used for the experiments, and age-matched Wistar-Kyoto rats (WKY) were used as a genetic control. Basal, forskolin-, and GppNHp-stimulated AC activities were not different between SHRSP and WKY in the 8-week-old and 25-week-old groups.

Molecular diversity and double regulatory mechanism of activation of phospholipase C in rat brain.

Whereas evidence for a G protein-dependent stimulation of phospholipase C (PLC) is abundant, reports on the inhibition of PLC through a G protein-mediated pathway have only recently begun to appear. In the present study, cerebral cortex membranes were chosen since they have a readily measurable Gpp[NH]p and Ca2+-stimulated PLC activity. Nanomolar concentrations of Gpp[NH]p, a hydrolysis-resistant GTP analogue, inhibited basal inositol 1,4,5-trisphosphate (IP3) production, with a maximum inhibition of 25% at 10 nM.

Negative chronotropic effect of botulinum toxin on neonatal rat cardiac myocytes.

We demonstrated that botulinum neurotoxin attenuated the spontaneous beating rate of cultured cardiac myocytes. Primary cultured cardiac myocytes were prepared from the ventricles of neonatal Wistar rats (1-3 days old). On 7 days after cell seeding, botulinum toxin type A incorporated into liposomes was added to the culture medium.

Effects of ondansetron on electrically evoked contraction in rat stomach fundus: possible involvement of 5-HT2B receptors.

This study examined the effects of ondansetron, an antagonist of the 5-hydroxytryptamine (5-HT3) receptor without 5-HT4 receptor agonistic activity. on electrically evoked contractions and acetylcholine release in rat stomach fundus strips. Ondansetron (10(-8)-10(-4) M) produced a concentration-dependent increase in the magnitude of the electrically evoked contraction, while it inhibited the release of acetylcholine induced by electrical field stimulation.

Involvement of tyrosine kinase in capacitative Ca2+ entry pathway in rat glioma C6 cells.

Capacitative Ca2+ entry, a main pathway of Ca2+ entry evoked by receptor activation, is widely confirmed in various types of cells. However, the mechanism of the activation of capacitative Ca2+ entry is unknown. We checked the several candidates for the mechanism of capacitative Ca2+ entry pathway in rat glioma C6 cells using thapsigargin (TG), a microsomal Ca(2+)-ATPase inhibitor.

Upregulation of expression of sarcoplasmic reticulum by TGF-beta 1 in cultured rat cardiac myocytes.

The effects of transforming growth factor-beta 1 (TGF-beta 1) on the function and structure of sarcoplasmic reticulum (SR) were studied in cultured neonatal rat cardiac myocytes. The cardiac myocytes at days 2 and 6 of culture exhibited spontaneous contraction; however, the rate of contraction increased and became regular, depending on culture day. Ryanodine and norepinephrine (NE) increased the rate of contraction and frequency of Ca2+ oscillations in myocytes at day 2 of culture.