Functional roles of 5-hydroxytryptamine 3/4 receptors in neurons of rat dorsal motor nucleus of the vagus.

In neurons of dorsal motor nucleus of the vagus that is involved in the gastric motility and possibly emesis, application of 5-hydroxytryptamine produces membrane depolarization, and suppresses spike-repolarization and spike-afterhyperpolarization, suggesting divergent effects of 5-hydroxytryptamine through activating multiple subtypes of 5-hydroxytryptamine receptors. However, only the role of 5-hydroxytryptamine 2A receptors has been established to be responsible for the depolarization, and the mechanisms underlying the modulation of spikes remain unknown although a role of 5-hydroxytryptamine 4 receptors was implicated in modulations of spikes. There is now increasing evidence for the role of 5-hydroxytryptamine receptors in neurons involved in generating emesis following administration of anticancer drug. Since antagonists of 5-hydroxytryptamine 3/4 receptors are widely used as anti-emetic drugs, we have reevaluated the functional roles of 5-hydroxytryptamine 3/4 receptors of dorsal motor nucleus of the vagus neurons, especially in modulating transient outward currents that are presumed to be involved in spike-repolarization and spike-afterhyperpolarization. Whole-cell patch-clamp recordings were made from the dorsal motor nucleus of the vagus neurons, which were identified by a retrograde tracing method with dextran-tetramethylrhodamine-lysine injected into a bundle of abdominal vagus nerves. Under a voltage-clamp condition, dorsal motor nucleus of the vagus neurons expressed a prominent A-like current. The activation of 5-hydroxytryptamine 3 receptors reversibly increased the resting membrane conductance while the activation of 5-hydroxytryptamine 4 receptors led to an almost irreversible decrease in the A-like current. A long-lasting suppression of A-like current by transient activation of 5-hydroxytryptamine 4 receptors would result in a long-lasting increase in the excitability of dorsal motor nucleus of the vagus neurons, which might be involved in generation of the long-lasting facilitation of gastric motility or in generation of the long-lasting gastric relaxation through the activation of enteric non-adrenergic non-cholinergic neurons as implicated in the delayed emesis induced by anticancer drugs.

Isolation and structural elucidation of a peptide derived from Edam cheese that inhibits beta-lactoglobulin transport.

A peptide that inhibits beta-lactoglobulin absorption in an in vitro Caco-2 cell model was isolated from Edam cheese. By 1H-NMR and N-terminal amino acid analyses, the active compound was identified as Asp-Lys-Ile-His-Pro-Phe. The sequence of the hexapeptide is the same as the amino acid sequence of residues 47-52 of beta-casein. The hexapeptide shows remarkable inhibition of beta-lactoglobulin transport at a concentration of 10(-7)M. The possibility exists that this peptide can be applied practically to the prevention of milk-sensitive allergy.

Isolation and characterization of a novel polysaccharide as a possible allergen occurring in wheat flour.

A new polysaccharide with a molecular weight of 5.0 x 10(4) was isolated as a possible wheat allergen from a water-soluble fraction of flour by affinity chromatography and gel filtration. The isolated polysaccharide was found to be a possible wheat allergen, as it bound specifically to IgE antibodies in the sera of patients allergic to the water-soluble fraction of flour. Chemically, the sugar moiety of the polysaccharide consisted of D-glucose and D-mannose with beta-1,4-linkages in a molar ratio of 4.4:1. Since this mannoglucan is thought to be stable in our body, it would act as a remaining allergen to cause a long-lasting allergic reaction to wheat flour.

4-Hydroxy-3-nitrophenylacetic and Sinapic Acids as Antibacterial Compounds from Mustard Seeds.

A methanol extract from yellow mustard seeds had antibacterial activity against Escherichia coli, Salmonella enteritidis, and Staphylococcus aureus. Two compounds with such activity were isolated from the extract. By instrumental analysis, the compounds were identified as 4-hydroxy-3-nitrophenylacetic and sinapic acids. Examination of the structure-activity relationship showed that the hydroxyl and nitro groups of the first compound were involved in the activity against all three species. The two methoxyl groups and the hydroxyl group in sinapic acid were effective against E. coli and all of the substituents of the benzene ring were effective against S. enteritidis. The presence of the propenoic group of the second compound was effective against S. aureus.

Seven acylated anthocyanins in the blue flowers of Hyacinthus orientalis.

Two novel anthocyanins, delphinidin 3-O-(6-O-cis-p-coumaroyl-beta-D-glucoside)-5-O-(6-O-malonyl-beta-D -glucoside) and petunidin 3-O-(6-O-trans-p-coumaroyl-beta-D-glucoside)-5-O-(6-O-malonyl-beta -D-glucoside) , were isolated from the blue flowers of Hyacinthus orientalis cv. Delft Blue. Five known acylated anthocyanins, namely, delphinidin 3-O-(6-O-trans-p-coumaroyl-beta-D-glucoside)-5-O-(6-O-beta-D-gluco side), delphinidin 3-O-(6-O-trans-caffeoyl-beta-D-glucoside)-5-O-(6-O-malonyl-beta-D- glucoside), delphinidin 3-O-(6-O-trans-p-coumaroyl-beta-D-glucoside)-5-O-(6-O-malonyl-beta -D-glucoside) , cyanidin 3-O-(6-O-trans-p-coumaroyl-beta-D-glucoside)-5-O-(6-O-malonyl-beta -D-glucoside) and pelargonidin 3-O-(6-O-trans-p-coumaroyl-beta-D-glucoside)-5-O-(6-O-malonyl-beta -D-glucoside) , were also isolated from these flowers. The complete structure of each compound was unambiguously determined by one- and two-dimensional NMR techniques.

[Changes of glucose uptake in vestibular and auditory nuclei induced by high perilymphatic potassium ion concentration--autoradiographic study].

Characteristic nystagmus could be provoked by introducing potassium ion into the unilateral perilymphatic space of healthy guinea pigs. At first, irritative nystagmus appeared for some time to the K+ introduced ear side, and then, it was followed by paralytic nystagmus which directed to the non introduced ear side. During this experiment, the excitabilities of the vestibular nuclei and the central auditory nuclei were investigated by [14C] deoxyglucose method. In the period of "irritative nystagmus", the increment of glucose uptake in the ipsilateral vestibular nucleus, especially in the superior, median and inferior part, was noticed more significantly than the contralateral vestibular nucleus. On the other hand, the period of "paralytic nystagmus" showed the significant increment of glucose uptake in all parts of the contralateral vestibular nucleus. As to the excitability of the central auditory nuclei, the significant decrement of glucose uptake, which was noticed in all periods of this experiment, was predominant in the ipsilateral cochlear nucleus and other superior auditory nuclei of the contralateral side.

The mechanism of irritative nystagmus and paralytic nystagmus. A histochemical study of the guinea pig's vestibular organ and an autoradiographic study of the vestibular nuclei.

To establish the difference of mechanism between irritative and paralytic nystagmus, alterations of Na-K-ATPase and succinic dehydrogenase activity in the vestibular sensorineural elements were investigated for 20 guinea pigs, and glucose uptake of the vestibular nuclei for 13 guinea pigs were measured by the [14C]-2-deoxy-D-glucose method. Irritative and paralytic nystagmus were experimentally provoked by introducing K+ into the perilymphatic space. From the results it was concluded that irritative nystagmus is provoked by increased excitability of vestibular sensory cells, while paralytic nystagmus is provoked by decreased excitability. However, the direction of nystagmus was eventually decided by the tonus imbalance between the bilateral vestibular nuclei. The ipsilateral vestibular nucleus was predominant during irritative nystagmus, while the contralateral vestibular nucleus was predominant during paralytic nystagmus.