Central neuropeptide Y induces proximal stomach relaxation via Y1 receptors in the dorsal vagal complex of the rat

Effects of neuropeptide Y (NPY) on motility of the proximal stomach was examined in anesthetized rats. Intragastric pressure was measured using a balloon situated in the proximal part of the stomach. Administration of NPY into the fourth ventricle induced relaxation of the proximal stomach in a dose-dependent manner. Administration of an Y1 receptor (Y1R) agonist [Leu31, Pro34]NPY induced a larger relaxation than NPY. The administration of an Y2 receptor agonist (NPY 13-36) did not induce significant changes in motility. Microinjections of [Leu31, Pro34]NPY into the caudal part of the dorsal vagal complex (DVC) induced relaxation of the proximal stomach. In contrast, similar injections into the intermediate part of the DVC increased IGP of the proximal stomach. Administration of NPY into the fourth ventricle did not induce relaxation after bilateral injections of the Y1R antagonist (1229U91) into the caudal DVC. These results indicate that NPY induces relaxation in the proximal stomach via Y1Rs situated in the DVC. Because bilateral vagotomy below the diaphragm abolished the relaxation induced by the administration of NPY into the fourth ventricle, relaxation induced by NPY is probably mediated by vagal preganglionic neurons. Intravenous injection of atropine methyl nitrate reduced relaxation induced by administration of NPY. Therefore, relaxation induced by NPY is likely mediated by peripheral cholinergic neurons.     

Occurrence of Crithidia Factors and Folic Acid in Various Bacteria

Crithidia factors and folic acid were found to be widely distributed in culture fluids and in cells of 27 species of bacteria, when cultured under aerobic conditions into the stationary phase. Most bacteria excreted more Crithidia factors and folic acid than they retained in their cells. One Crithidia factor produced by Serratia indica and one produced by Bacillus cereus differed from biopterin in their chromatographic behavior. The factor excreted by S. indica appeared to be a 2-amino-4-hydroxy-6-substituted pteridine on the basis of KMnO(4) oxidation and ultraviolet absorption spectra. One of the folate compounds excreted by this organism was shown to be identical to 5,10-methylidynetetrahydrofolic acid by bioautography.     

Fractionation of Cigarette Smoke Components and Some Low Boiling Point Nitrogenous Compounds (I)

The chemical components of cigarette smoke produced in constant volume continuous smoking by an artificial smoking device were systematically fractionated into basic, acidic, neutral, phenolic, carbonyl and mercuric chloride-precipitable compounds. From the low boiling basic fractions ammonia, methylamine and ethylamine were qualitatively identified by paper chromatography, and pyridine and nicotine were isolated and identified by elementary analyses, mixed examinations and infrared spectra. An unidentified substance having elementary analysis values of C, 29.40; H, 1.93; N, 22.40 as picrate (m.p. 250°C, dec.) was isolated.     

Studies on the Chemical Evaluation of Tobacco Quality

Various organoleptic characteristics of cigarette smoke, such as aroma, taste, harshness, offensive odor and taste, strength and dryness, were measured by sensory test using more than fifty kinds of flue-cured tobacco leaves. The results were compared with those of chemical and gas chromatographic analyses of the particulate matter in the smoke. The correlations between each evaluation characteristic and each analytical value were computed and simple equations for tobacco evaluation were set up. The equations obtained were considered to be available for the evaluation of tobacco quality instead of the sensory test, although their applications to lowgrade samples seemed to need further modifications.     

A Naturally Occurring Null Variant of the NMDA Type Glutamate Receptor NR3B Subunit Is a Risk Factor of Schizophrenia

Hypofunction of the N-methyl-D-aspartate type glutamate receptor (NMDAR) has been implicated in the pathogenesis of schizophrenia. Here, we investigated the significance of a common human genetic variation of the NMDAR NR3B subunit that inserts 4 bases within the coding region (insCGTT) in the pathogenesis of schizophrenia. The cDNA carrying this polymorphism generates a truncated protein, which is electrophysiologically non-functional in heterologous expression systems. Among 586 schizophrenia patients and 754 healthy controls, insCGTT was significantly overrepresented in patients compared to controls (odds ratio = 1.37, p = 0.035). Among 121 schizophrenia patients and 372 healthy controls, genetic analyses of normal individuals revealed that those carrying insCGTT have a predisposition to schizotypal personality traits (F_1,356 = 4.69, p = 0.031). Furthermore, pre-pulse inhibition, a neurobiological trait disturbed in patients with schizophrenia, was significantly impaired in patients carrying insCGTT compared with those with the major allele (F_1,116 = 5.72, p = 0.018, F_1,238 = 4.46, p = 0.036, respectively). These results indicate that a naturally occurring null variant in NR3B could be a risk factor of schizophrenia.     

CD73-generated adenosine promotes osteoblast differentiation

CD731 is a GPI-anchored cell surface protein with ecto-5'-nucleotidase enzyme activity that plays a crucial role in adenosine production. While the roles of adenosine receptors (AR) on osteoblasts and osteoclasts have been unveiled to some extent, the roles of CD73 and CD73-generated adenosine in bone tissue are largely unknown. To address this issue, we first analyzed the bone phenotype of CD73-deficient (cd73(-/-)) mice. The mutant male mice showed osteopenia, with significant decreases of osteoblastic markers. Levels of osteoclastic markers were, however, comparable to those of wild-type mice. A series of in vitro studies revealed that CD73 deficiency resulted in impairment in osteoblast differentiation but not in the number of osteoblast progenitors. In addition, over expression of CD73 on MC3T3-E1 cells resulted in enhanced osteoblastic differentiation. Moreover, MC3T3-E1 cells expressed adenosine A(2A) receptors (A(2A)AR) and A(2B) receptors (A(2B)AR) and expression of these receptors increased with osteoblastic differentiation. Enhanced expression of osteocalcin (OC) and bone sialoprotein (BSP) observed in MC3T3-E1 cells over expressing CD73 were suppressed by treatment with an A(2B)AR antagonist but not with an A(2A) AR antagonist. Collectively, our results indicate that CD73 generated adenosine positively regulates osteoblast differentiation via A(2B)AR signaling.     

A novel marker for terminal Schwann cells,homocysteine-responsive ER-resident protein,as isolated by a single cell PCR-differential display

Terminal Schwann cells (TSCs) that cover motor neuron terminals are known to play important roles in maintaining neuromuscular junctions, as well as in the repair process after nerve injury. However, molecular characteristics of TSCs remain unknown, because of the difficulties in analyzing them due to their paucity. We have established a method of selectively and efficiently collecting TSCs so that cDNA analysis can be done properly. The expression of 1-2% of whole mRNAs was compared between myelinating Schwann cells (MSCs) and TSCs, and it turned out that approximately one-third of the bands could be categorized as cell-type-specific bands. TSCs thus constitute a distinct entity from the viewpoint of gene expression. As one of the cDNA clones belonging to TSC-specific bands was identified homocysteine-responsive ER-resident protein (Herp), and in situ hybridization confirmed that Herp mRNA is expressed in TSCs on motor nerve terminals but not in MSCs, both in developing and adult rats. In conclusion, we have been able to identify Herp as a novel molecular marker for TSCs.     

Suppression of vagal motor activities evokes laryngeal afferent-mediated inhibition of gastric motility

We previously reported that the activation of water-responsive afferents in the superior laryngeal nerve was responsible for the inhibition of gastric motility. The present study was undertaken to clarify the roles of the vagal preganglionic neurons responsible for laryngeal afferent-mediated inhibition of gastric motility. Intravenous injection of atropine abolished the inhibition of motility in both the distal and the proximal stomach induced by water administration into the larynx. The neurons in the dorsal motor nucleus of the vagus (DMV), which project to the abdominal viscera, were exclusively inhibited by water administration. Taken together, inhibition of neurons in the DMV induces inhibition of gastric motility evoked by laryngeal water-responsive afferents via a cholinergic pathway. Because chemical lesions of the intermediate DMV, but not the caudal DMV, abolished the inhibition of the distal stomach motility induced by water administration, the intermediate DMV is responsible for the inhibition shown in the distal stomach.