Arabinogalactan protein polysaccharide chains are required for normal biogenesis of plasmodesmata.

Arabinogalactan proteins (AGPs) are a plant-specific family of extracellular proteoglycans characterized by large and complex galactose-rich polysaccharide chains. Functional elucidation of AGPs, however, has been hindered by the high degree of redundancy of AGP genes. To uncover as yet unexplored roles of AGPs in Arabidopsis, a mutant of Hyp O-galactosyltransferase (HPGT), a critical enzyme that catalyzes the common initial step of Hyp-linked arabinogalactan chain biosynthesis, was used. Here we show, using the hpgt1,2,3 triple mutant, that a reduction in functional AGPs leads to a stomatal patterning defect in which two or more stomata are clustered together. This defect is attributed to increased and dysregulated symplastic transport following changes in plasmodesmata structure, such that highly permeable complex branched plasmodesmata with cavities in branching parts increased in the mutant. We also found that the hpgt1,2,3 mutation causes a reduction of cellulose in the cell wall and accumulation of pectin, which controls cell wall porosity. Our results highlight the importance of AGPs in the correct biogenesis of plasmodesmata, possibly acting through the regulation of cell wall properties surrounding the plasmodesmata.

Peptide ligand-mediated trade-off between plant growth and stress response.

Deciding whether to grow or to divert energy to stress responses is a major physiological trade-off for plants surviving in fluctuating environments. We show that three leucine-rich repeat receptor kinases (LRR-RKs) act as direct ligand-perceiving receptors for PLANT PEPTIDE CONTAINING SULFATED TYROSINE (PSY)-family peptides and mediate switching between two opposing pathways. By contrast to known LRR-RKs, which activate signaling upon ligand binding, PSY receptors (PSYRs) activate the expression of various genes encoding stress response transcription factors upon depletion of the ligands. Loss of PSYRs results in defects in plant tolerance to both biotic and abiotic stresses. This ligand-deprivation-dependent activation system potentially enables plants to exert tuned regulation of stress responses in the tissues proximal to metabolically dysfunctional damaged sites where ligand production is impaired.

Shoot-to-root mobile CEPD-like 2 integrates shoot nitrogen status to systemically regulate nitrate uptake in Arabidopsis.

Plants modulate the efficiency of root nitrogen (N) acquisition in response to shoot N demand. However, molecular components directly involved in this shoot-to-root communication remain to be identified. Here, we show that phloem-mobile CEPD-like 2 (CEPDL2) polypeptide is upregulated in the leaf vasculature in response to decreased shoot N status and, after translocation to the roots, promotes high-affinity uptake and root-to-shoot transport of nitrate. Loss of CEPDL2 leads to a reduction in shoot nitrate content and plant biomass. CEPDL2 contributes to N acquisition cooperatively with CEPD1 and CEPD2 which mediate root N status, and the complete loss of all three proteins severely impairs N homeostasis in plants. Reciprocal grafting analysis provides conclusive evidence that the shoot CEPDL2/CEPD1/2 genotype defines the high-affinity nitrate uptake activity in root. Our results indicate that plants integrate shoot N status and root N status in leaves and systemically regulate the efficiency of root N acquisition.

Lercanidipine rescues hippocampus pyramidal neurons from mild ischemia-induced delayed neuronal death in SHRSP.

Stroke-prone spontaneously hypertensive rats (SHRSPs) are vulnerable to ischemia and delayed neuronal death (DND) of hippocampus pyramidal cells when bilateral carotid arteries are occluded for only 10 min. Since this occlusion induces just mild ischemia, the resulting DND may be an appropriate animal model for dementia in patient with essential hypertension exposed to small ischemic insults. This study was designed to compare the effects of the antihypertensive drugs lercanidipine, nicardipine, lisinopril, valsartan, and hydralazine on occlusion-induced DND in SHRSPs. Drugs were administered for 2 weeks, from 15 to 17 weeks of age. 0.1% Nicardipine and 0.01 or 0.03% lercanidipine were administered in the SP diet (about 61.3, 5.7, and 18.8 mg/kg/day, respectively), and the remaining drugs were administered at 10 mg/kg/day using the mini-osmotic pump. The animals were operated on at 16 weeks of age, and DND was analyzed by histological examination 1 week later. Systolic blood pressure was measured at 15, 16, and 17 weeks of age. For chronic treatment, Calcium-channel blockers were administered from 8 to 17 weeks of age. All antihypertensive drugs significantly lowered systolic blood pressure at 16 weeks of age. Hydralazine and lisinopril were associated with the greatest reduction; however, lercanidipine, nicardipine, and valsartan effectively reduced systolic blood pressure to within a medium range. DND was significantly inhibited only by 0.03% lercanidipine. Chronic treatment with 0.03% lercanidipine also protected pyramidal neurons. The results of this study demonstrate that the long-acting, lipophilic Calcium-channel blocker lercanidipine inhibits occlusion-induced DND in SHRSPs and that lercanidipine may effectively reduce dementia induced by small ischemic insults in patients with essential hypertension.

Blood pressure-independent factors determine the susceptibility to delayed neuronal death in the stroke-prone spontaneously hypertensive rats.

The stroke-prone spontaneously hypertensive rat (SHRSP) is vulnerable to delayed neuronal death (DND) in the CA1 subfield of the hippocampus after the transient forebrain ischemia by the occlusion of the bilateral carotid arteries. The present study was designed to show that the genetic factors independent of high blood pressure contributed to the high incidence of DND in SHRSP. Male rats of the four strains, SHRSP/Izm, SHRSP/Ngsk, SHR/Izm and a congenic strain for the blood pressure quantitative trait locus on chromosome 1 [SHRSP.WKY-(D1Wox29-D1Arb21)/Izm]were used in the experiments. At 13 weeks of age, the bilateral carotid arteries of rats were occluded for 10 min under anesthesia with their body temperature kept at 37 degreeC. Seven days after the transient ischemia, the loss of the pyramidal cells in the CA1 was evaluated histologically. In some experiments, the blood flow was monitored with a laser Doppler flowmeter during the transient ischemia. The blood pressure in SHRSP/Izm was significantly greater than that in the other three strains. The incidence of DND, however, was not significantly different among SHRSP/Izm, SHRSP/Ngsk and the congenic strain (82, 74 and 65%, respectively), while SHR/Izm showed a significantly lower incidence (20 percent). Neither a significant correlation between the incidence of DND and the blood flow reduction during the occlusion, nor a significant inter-strain difference in the blood flow reduction was observed. The genetic factors independent of high blood pressure may contribute to the greater susceptibility to DND in SHRSP.

Scavenger receptor B2 is a cellular receptor for enterovirus 71.

Enterovirus 71 (EV71) belongs to human enterovirus species A of the genus Enterovirus within the family Picornaviridae. EV71, together with coxsackievirus A16 (CVA16), are most frequently associated with hand, foot and mouth disease (HFMD). Although HFMD is considered a mild exanthematous infection, infections involving EV71, but not CVA16, can progress to severe neurological disease, including fatal encephalitis, aseptic meningitis and acute flaccid paralysis. In recent years, epidemic and sporadic outbreaks of neurovirulent EV71 infections have been reported in Taiwan, Malaysia, Singapore, Japan and China. Here, we show that human scavenger receptor class B, member 2 (SCARB2, also known as lysosomal integral membrane protein II or CD36b like-2) is a receptor for EV71. EV71 binds soluble SCARB2 or cells expressing SCARB2, and the binding is inhibited by an antibody to SCARB2. Expression of human SCARB2 enables normally unsusceptible cell lines to support EV71 propagation and develop cytopathic effects. EV71 infection is hampered by the antibody to SCARB2 and soluble SCARB2. SCARB2 also supports the infection of the milder pathogen CVA16. The identification of SCARB2 as an EV71 and CVA16 receptor contributes to a better understanding of the pathogenicity of these viruses.

[Analysis of hexachlorobenzene in Food Red Nos. 104 (phloxine) and 105 (rose Bengal) by GC-ECD].

A simple and rapid method using electron capture detector gas chromatography (GC-ECD) was developed for the determination of hexachlorobenzene (HCB) in Food Red Nos. 104 and 105. The sample was dissolved in water and HCB was extracted with hexane. The GC-ECD operating conditions were as follows: column, InertCap 5 MS/NP (30 m x 0.25 mm i. d. with 0.25 microm film thickness); oven temperature, 60 degrees C(1 min)-->20 degrees C/min-->150 degrees C(10 min)-->20 degrees C/min-->280 degrees C(5 min); inlet temperature, 260 degrees C; detector temperature, 300 degrees C; carrier gas, nitrogen (constant press 25 psi); inlet mode, splitless. For the evaluation of the method, HCB spiked into R104 and R105 at the levels of 2 microg/g and 5 microg/g was determined in replicate in five laboratories. Mean recoveries of HCB from R104 and R105 were 98.2-103.7%. Repeatability relative standard deviation values were 2.9-6.0% and reproducibility relative standard deviation values were 4.2-9.3%. HORRAT value was less than one. From these results, the validity of this method was confirmed.

Quantitative analysis of delayed neuronal death in the hippocampal subfields of SHRSP and SHR.

Transient forebrain ischemia and reperfusion induces delayed neuronal death (DND) in the hippocampal Cornu Ammonis 1 (CA1) subfield of stroke-prone spontaneously hypertensive rat (SHRSP). The vulnerability to DND is potentially related to the genetic susceptibility to stroke in this strain. To elucidate the mechanism of DND in SHRSP, however, it is essential to establish a method for quantitative evaluation of DND, which is not available yet. Male SHRSPs and spontaneously hypertensive rats (SHRs) at 12 weeks of age were used in the experiment. The bilateral common carotid arteries were surgically occluded with aneurysmal clips for 10 min. The brain was taken out 7 days after the experiment of the transient ischemia, and was sliced into serial coronal sections. Quantitative estimation of the number of viable pyramidal cells in the CA1 and CA2/3 subfields was performed based on the stereology with a random and systematic sampling. The transient ischemia and reperfusion (TIR) significantly reduced the number of viable pyramidal cells in CA1 of SHRSP (61000 +/- 20100 in TIR vs. 128500 +/- 21900 in the sham-operation, P < 0.000001 by Student's t-test), while no significant difference was observed in SHR (140300 +/- 30800 in TIR vs. 128200 +/- 16700 in the sham-operation, P = 0.35). Further analysis revealed a dorsal-ventral gradient in the distribution of DND in CA1 of SHRSP with the most severe change in the dorsal area. The quantitative measurement using a stereological method is useful in the precise evaluation of DND in SHRSP. This method can be applied in the studies of effects of medical treatments on the 'ischemia/reperfusion' insult.

Mild ischemia produces hippocampal neuronal death in stroke-prone spontaneously hypertensive rats.

The blood flow in the hippocampus of stroke-prone spontaneously hypertensive rats (SHRSPs) and Wistar Kyoto (WKY) rats during occlusion of the carotid arteries was examined because it has been previously found that 2-vessel occlusion (2-VO) induces delayed neuronal death (DND) in the pyramidal cells of the CA1 hippocampal area in SHRSPs but not in WKY rats. DND was also examined in 4-week-old SHRSPs, which are as yet normotensive, in order to reveal the involvement of the development and maintenance of severe hypertension in DND in SHRSPs. Before, during and after occlusion, the blood flow in the hippocampus was continuously monitored by laser Doppler flowmetry, wherein the probe was connected to a plastic fiber that was implanted in the CA1 subfield of animals. The change in blood flow was determined by comparing its rate during occlusion to the preoperative value. DND was confirmed by histological examination at 7days after the operation. The rate of blood flow during 2-VO was similar between the SHRSPs (42.6% +/- 5.3%) and WKY rats (49.0% +/- 14.3%). WKY rats that underwent 4-vessel occlusion (4-VO), which induces DND in WKY rats, exhibited a severely decreased blood flow of 13.7% of the preoperative value. DND was also observed in 4-week-old SHRSPs that underwent 2-VO, and the incidence was identical to that in 12-week-old SHRSPs. The present results suggest that the DND that occurs in SHRSPs due to 2-VO is not a result of the more severe reduction in blood supply during the occlusion than that in WKY rats, and secondary damage due to severe hypertension but is caused by some genetic factors due to which the pyramidal neurons of SHRSPs are more vulnerable to ischemic insult than those of WKY rats are.

Possible protection of sinusoidal endothelial cells by endothelin B receptor during hepatic warm ischemia-reperfusion.

PURPOSE: Endothelins (ETs) are important regulators of the hepatic microcirculation. We investigated the pure biological roles of endothelin B receptors (ETB-Rs) on hepatic warm ischemia-reperfusion (I/R) injury using ETB-R deficient spotting lethal (sl) rats. METHODS: Homozygous (sl/sl) and wild-type (+/+) rats were exposed to 60 min of 92% partial hepatic ischemia and then were killed at 2, 6, and 24 h, and 3 and 7 days after reperfusion. We measured the serum alanine aminotransferase (ALT) levels to assess hepatocyte injury, and the serum hyaluronic acid (HA) levels and factor VIII-related antigen (FVIIIRAg) staining to assess sinusoidal endothelial cell (SEC) injury. We also measured the concentrations of ET-1 and nitrite (NO2-) and nitrate (NO3-) of liver tissue samples. RESULTS: Although no significant difference was observed in the ALT levels, the HA levels were significantly elevated at an early stage after reperfusion in the sl/sl rats. Regarding FVIIIRAg staining, positive SECs were enhanced in the sl/sl rats. The ET-1 levels were also significantly elevated at an early stage after reperfusion in the sl/sl rats. Regarding the NO2- and NO3- levels, no significant difference was observed. CONCLUSION: Endothelin B receptor was shown to have a protective effect on SECs through the inhibition of ET-1 during hepatic warm I/R injury.

Neuroprotective effect of pentosan polysulphate on ischemia-related neuronal death of the hippocampus.

Pentosan polysulphate (PPS) negatively charged sulphated glycosaminoglycan was studied in ischemia-related hippocampal neuronal death and compared with a low molecular weight of heparin, named dalteparin in rats. Transient global ischemia was produced by four vessel-occlusion, the occlusion of the bilateral common carotid arteries following the electrocautherization of the vertebral arteries. 3mg/kg of PPS or 300IU/kg of dalteparin was administered i.v. immediately after 7min-occlusion/reperfusion. Seven days after the operation, the animals were perfused with 4% paraformaldehyde, and paraffinized coronal brain sections measuring 6microm in thickness were stained with hematoxylin and eosin. Neuronal damage was then estimated as a ratio of the number of degenerated neurons to that of both the surviving and degenerated neurons in three distinct area of the CA1 subfield. The ratio of neuronal death increased with the length of the occlusion-time, at 5, 7 and 10min. Both PPS and dalteparin significantly inhibited the neuronal damage induced by 7min-occlusion. These results demonstrated that both PPS and dalteparin could thus protect brain neurons against ischemia/reperfusion-induced damage thus suggesting that they may be potentially useful therapeutic agents for acute ischemic stroke.

Expression of MCP-1 in the hippocampus of SHRSP with ischemia-related delayed neuronal death.

1. The expression of monocyte chemoattractant protein-1 (MCP-1) was examined in stroke-prone spontaneously hypertensive rats with transient global ischemia in order to study the involvement of the infiltration of blood monocytes in the mechanism of ischemia-related neuronal death. 2. The brains of the animals with occlusion of the bilateral carotid arteries for 10 min were removed at 8 h, 1, 2, 4 and 7 days after reperfusion. Frozen sections were used for in situ hybridization and tissue specimens from the hippocampus and the cerebral cortex were used to measure the concentration of MCP-1 by ELISA. 3. No MCP-1 mRNA was detected in the hippocampus of the sham group animals. One day after ischemia-reperfusion, MCP-1 mRNA was clearly expressed in the CA4 subfield and the molecular layer of the dentate gyrus, while it was slightly expressed in the lacnosum moleculare of the CA1 subfield. A dramatic expression was demonstrated in the entire CA1 subfield at 2 days after the operation. Most of the cells expressing MCP-1 were astrocytes. At 4 and 7 days after reperfusion, no MCP-1 mRNA was detected in the hippocampus. The concentration of MCP-1 protein dramatically increased in the hippocampus at 2 days after reperfusion. 4. Taken together with the findings of our previous study showing an increased permeability of the blood-brain barrier in the hippocampus from 12 h after ischemia-reperfusion, the astrocytes expressing MCP-1 might therefore induce the migration of monocytes into the brain parenchyma. As a result, such astrocytes expressing MCP-1 may therefore be related to the pathological events of delayed neuronal death in the pyramidal neurons.

[Current advances in leprosy research activities].

Due to the advent of multi-drug therapy (MDT) recommended by the WHO, for the treatment of leprosy, presently, leprosy is regarded as a "curable disease". The number of new cases in Japan is relatively very low, due to which the disease is likely to be neglected, but on scientific grounds, there is a necessity to perform in depth studies. Leprosy caused by M. leprae is still unclear on various aspects including transmission, immunology, nerve damage etc. Here we introduce the recent advances in the field of basic leprosy research.

Role of the polypeptide region of a 33kDa mycobacterial lipoprotein for efficient IL-12 production.

Mycobacterium leprae lipoprotein, LpK, induced IL-12 production from human monocytes. To determine the components essential for cytokine production and the relative role of lipidation in the activation process, we produced lipidated and non-lipidated truncated forms of LpK. While 0.5nM of lipidated LpK-a having N-terminal 60 amino acids of LpK produced more than 700pg/ml IL-12 p40, the non-lipidated LpK-b having the same amino acids as that of LpK-a required more than 20nM of the protein to produce an equivalent dose of cytokine. Truncated protein having the C-terminal 192 amino acids of LpK did not induce any cytokine production. Fifty nanomolar of the synthetic lipopeptide of LpK produced only about 200pg/ml IL-12. Among the truncated LpK, only LpK-a and lipopeptide stimulated NF-kB-dependent reporter activity in TLR-2 transfectant. However, when monocytes were stimulated with lipopeptide in the presence of non-lipidated protein, they produced IL-12 synergistically. Therefore, both peptide regions of LpK and lipid residues are necessary for efficient IL-12 production.

Increases in serum nitrite and nitrate of a few-fold adversely affect the outcome of pregnancy in rats.

The objective of this study was to evaluate serum nitrite and nitrate (nitrite/nitrate) concentrations that affect adversely pregnancy outcome. Pregnant rats, from day 2 to day 8 of pregnancy, were daily given subcutaneously several doses (5, 10, and 30 mg/rat) of diethylenetriamine-nitric oxide (DETA/NO). Serum nitrite/nitrate concentrations were measured using an HPLC system. Serum nitrite/nitrate concentrations increased dose-dependently with DETA/NO. Effects of DETA/NO on pregnancy outcome were assessed on day 14 of pregnancy. In rats given 5 mg DETA/NO, there was a significant increase in serum nitrite/nitrate concentrations (49.2 vs 24.6 micromol/l, P<0.001), and both placental weight and fetal weight decreased compared to control rats. Macroscopic bleeding in placenta was frequently observed in rats given DETA/NO. We further studied effects of DETA/NO on cultured trophoblastic BeWo cells. DETA/NO added to the culture medium increased nitrite/nitrate concentrations in the medium in a dose-dependent manner. Nitrite/nitrate concentrations in the medium over four times the concentration of control decreased progesterone in the medium at 24 h after the application of DETA/NO. The hormonal secretion was not affected by DETA only. This study shows for the first time nitrite/nitrate concentrations affecting adversely pregnancy outcome and function of the trophoblastic cells.

Warfarin reduces the incidence of osteonecrosis of the femoral head in spontaneously hypertensive rats.

In this study, we investigated the effects of warfarin potassium on the incidence of the femoral head osteonecrosis in spontaneously hypertensive rats (SHR). Twenty-four SHRs were divided into two equal groups, one given normal water (water group) and another provided with water containing warfarin (warfarin group). We compared the two groups histologically and observed the incidence of osteonecrosis. We also studied 17 Wistar Kyoto rats (WKY) to compare with SHR. Coagulation time, platelet count, and protein C activity were measured. Immunohistochemistry was also performed using endothelial nitric oxide synthetase (eNOS) antibody to investigate the function of endothelial cells. The incidence of osteonecrosis was significantly less in the warfarin group (10.5%) than in the water group (52.6%). Coagulation time was significantly longer in the warfarin group than the water group. Platelet count and protein C activity were not statistically different between the warfarin group and the water group. Results of immunohistochemistry revealed that endothelial cells in the femoral head were positive for eNOS in WKY but not in SHR. Our results indicated that warfarin reduced the incidence of femoral head necrosis in SHR.

Role of endothelin ETA and ETB receptors in the guinea-pig urinary bladder contraction.

The distribution and function of endothelin receptors in the guinea-pig urinary bladder were examined. Specific [125I]endothelin-1 binding sites with both the endothelin ET(A) and ET(B) receptor subtypes were distributed in the muscle layer. Endothelin-1 elicited a tonic contraction which was inhibited by cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ123) but not by N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine (BQ788) and which was inhibited more strongly by a combination of BQ123 and BQ788. Sarafotoxin S6c elicited a contraction which was abolished by BQ788. The concentration of endothelin-1 in the muscle layer was 707.0+/-67.5 pg/g wet weight. Thus, endothelin-1 may regulate muscle tone via both subtypes of endothelin receptors in an autocrine manner in the guinea-pig urinary bladder.

A new-generation apparatus for studying memory-related performance in mice.

1. We developed a new kind of food search test that can measure murine nocturnal memory without handling hard work for setting up. 2. This apparatus has four food stations, but only one station had accessible food at any time. The one station with accessible food was changed at 4-h intervals. 3. We compared the performance of transient forebrain global Ischemic mice, which are a hippocampal lesion model, with the performance of control C57BL/6J mice. 4. The correct visit ratio, i.e., the ratio of the number of visits to the correct food station to the number of visits to all stations, gradually increased in the control mice, but did not change in the Ischemic mice. 5. This new system was demonstrated to be an additional and useful tool for studying memory-related performance in mice.

Involvement of 5-hydroxytryptamine4 receptor in the exacerbation of neuronal loss by psychological stress in the hippocampus of SHRSP with a transient ischemia.

A transient forebrain ischemia produced a delayed neuronal death of the hippocampus pyramidal cells in stroke-prone spontaneously hypertensive rats (SHRSP). Long term exposure of rats to stress has been reported to induce deleterious effects on the brain including morphological neuronal degeneration in the hippocampus. The present study was designed to examine the effects of psychological and physical stress on the ischemia-related neuronal death and the effects of 5-hydroxytryptamine(4) (5-HT(4)) receptor antagonist. SHRSP were exposed to the psychological or physical stress for 60 min in the communication box once or repeatedly for 3 days and occluded. SB204070, a 5-HT(4) receptor antagonist was injected before the occlusion. Seven days after the occlusion, the number of the neurons damaged morphologically was examined. A transient bilateral carotid occlusion produced a neuronal death of the CA1 subfield of the hippocampus in a time-dependent manner between 3 and 10 min. A 4 min occlusion induced very little morphological damage and a 5 min one produced a significant neuronal death. Exposure of rats to the psychological stress during 60 min for 3 days before the ischemic insults damaged the pyramidal cells by 4 min ischemia much more than without stress. Physical stress daily for 3 times also increased the damaged neurons. Pretreatment of SB204070 0.1 mg/kg after the stress exposure for 3 days significantly decreased the neuronal damage exacerbated by the stress exposure; however, it did not alter the damage induced by 4 or 10 min occlusion without stress. These results suggest that the repeated exposure of animals to the stress dramatically exacerbates the neuronal death by a transient ischemia and the 5-HT(4) receptor may be involved in the stress-induced exacerbating mechanism of the neuronal damage.

In vivo assessment of acceleration of motor activity associated with acetylcholine release via 5-hydroxytryptamine4 receptor in dog intestine.

Effect of mosapride, a benzamide, on the motor activity associated with the release of endogenous acetylcholine (ACh) from enteric neurons was examined in the ileum of anesthetized dogs using an in vivo microdialysis method and compared with the effect of 5-hydroxytryptamine (5-HT). Intraarterial administration of 5-HT accelerated intestinal motor activity and increased the concentration of dialysate ACh, and the responses were inhibited by SB204070, a specific 5-HT4-receptor antagonist, but were apparently not affected by methiothepin, ketanserin and granisetron. Intraarterial administration of mosapride, a prokinetic benzamide, accelerated intestinal motor activity and the concentration of dialysate ACh increased. The effects of mosapride were antagonized by SB204070. Specific [125I]SB207710 binding was observed in the myenteric and submucosal plexuses and muscle layers of dog ileum by in vitro receptor autoradiography. High densities of [125I]SB207710 binding sites were detected in the myenteric and submucosal plexuses. Mosapride as well as SB204070 inhibited [125I]SB207710 binding. Thus, in the whole body of dogs, 5-HT and mosapride accelerated the intestinal motor activity due to the increases in ACh release mediated by stimulation of the 5-HT4 receptor.