Non-genomic action of vitamin D3 on N-methyl-D-aspartate and kainate receptor-mediated actions in juvenile gonadotrophin-releasing hormone neurons
REPRODUCTION FERTILITY AND DEVELOPMENT
Authors: Bhattarai, Pravin; Bhattarai, Janardhan P.; Kim, Min Sun; Han, Seong Kyu
Vitamin D is a versatile signalling molecule that plays a critical role in calcium homeostasis. There are several studies showing the genomic action of vitamin D in the control of reproduction; however, the quick non-genomic action of vitamin D at the hypothalamic level is not well understood. Therefore, to investigate the effect of vitamin D on juvenile gonadotrophin-releasing hormone (GnRH) neurons, excitatory neurotransmitter receptor agonists N-methyl-D-aspartate (NMDA, 30M) and kainate (10M) were applied in the absence or in the presence of vitamin D3 (VitaD3, 10nM). The NMDA-mediated responses were decreased by VitaD3 in the absence and in the presence of tetrodotoxin (TTX), a sodium-channel blocker, with the mean relative inward current being 0.56 +/- 0.07 and 0.66 +/- 0.07 (P<0.05), respectively. In addition, VitaD3 induced a decrease in the frequency of gamma-aminobutyric acid mediated (GABAergic) spontaneous postsynaptic currents and spontaneous postsynaptic currents induced by NMDA application with a mean relative frequency of 0.595 +/- 0.07 and 0.56 +/- 0.09, respectively. Further, VitaD3 decreased the kainate-induced inward currents in the absence and in the presence of TTX with a relative inward current of 0.64 +/- 0.06 and 0.68 +/- 0.06, respectively (P<0.05). These results suggest that VitaD3 has a non-genomic action and partially inhibits the NMDA and kainate receptor-mediated actions of GnRH neurons, suggesting that VitaD3 may regulate the hypothalamic-pituitary-gonadal (HPG) axis at the time of pubertal development.
Xenin Augments Duodenal Anion Secretion via Activation of Afferent Neural Pathways
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Authors: Kaji, Izumi; Akiba, Yasutada; Kato, Ikuo; Maruta, Koji; Kuwahara, Atsukazu; Kaunitz, Jonathan D.
Xenin-25, a neurotensin (NT)-related anorexigenic gut hormone generated mostly in the duodenal mucosa, is believed to increase the rate of duodenal ion secretion, because xenin-induced diarrhea is not present after Roux-en-Y gastric bypass surgery. Because the local effects of xenin on duodenal ion secretion have remained uninvestigated, we thus examined the neural pathways underlying xenin-induced duodenal anion secretion. Intravenous infusion of xenin-8, a bioactive C-terminal fragment of xenin-25, dose dependently increased the rate of duodenal HCO (3) (-) secretion in perfused duodenal loops of anesthetized rats. Xenin was immunolocalized to a subset of enteroendocrine cells in the rat duodenum. The mRNA of the xenin/NT receptor 1 (NTS1) was predominantly expressed in the enteric plexus, nodose and dorsal root ganglia, and in the lamina propria rather than in the epithelium. The serosal application of xenin-8 or xenin-25 rapidly and transiently increased short-circuit current in Ussing-chambered mucosa-submucosa preparations in a concentration-dependent manner in the duodenum and jejunum, but less so in the ileum and colon. The selective antagonist for NTS1, substance P (SP) receptor (NK1), or 5-hydroxytryptamine (5-HT) (3), but not NTS2, inhibited the responses to xenin. Xenin-evoked Cl-secretion was reduced by tetrodotoxin (TTX) or capsaicin-pretreatment, and abolished by the inhibitor of TTX-resistant sodiumchannel Nav1.8 in combination with TTX, suggesting that peripheral xenin augments duodenal HCO3- and Cl- secretion through NTS1 activation on intrinsic and extrinsic afferent nerves, followed by release of SP and 5-HT. Afferent nerve activation by postprandial, peripherally released xeninmay account for its secretory effects in the duodenum.