High Salt Upregulates Ca-Sensing Receptor Expression and Ca-Induced Relaxation of Contracted Mesenteric Arteries from Dahl Salt-Sensitive Rats.

High Ca lowers blood pressure in hypertension, but the mechanism is not clear. The missing link may be the perivascular sensory nerve Ca-sensing receptor (CaSR) that mediates a vasodilator system after activation by interstitial Ca Our results show that high salt increased CaSR expression in mesenteric arteries as well as Ca relaxation of contracted mesenteric arteries from salt-sensitive (SS) rats. The CaSR was expressed as a doublet (≈120-150 kDa) in arteries from animals fed a high-salt diet for 1-4 weeks.

Protein Kinase C Downregulation Enhanced Extracellular Ca-Induced Relaxation of Isolated Mesenteric Arteries from Aged Dahl Salt-Sensitive Rats.

The Ca-sensing receptor (CaSR) detects small changes in extracellular calcium (Ca ) concentration ([Ca]) and transduces the signal into modulation of various signaling pathways. Ca-induced relaxation of isolated phenylephrine-contracted mesenteric arteries is mediated by the CaSR of the perivascular nerve. Elucidation of the regulatory mechanisms involved in vascular CaSR signaling may provide insights into the physiologic functions of the receptor and identify targets for the development of new treatments for cardiovascular pathologies such as hypertension.

Gαi/o-dependent Ca(2+) mobilization and Gαq-dependent PKCα regulation of Ca(2+)-sensing receptor-mediated responses in N18TG2 neuroblastoma cells.

A functional Ca(2+)-sensing receptor (CaS) is expressed endogenously in mouse N18TG2 neuroblastoma cells, and sequence analysis of the cDNA indicates high homology with both rat and human parathyroid CaS cDNAs. The CaS in N18TG2 cells appears as a single immunoreactive protein band at about 150 kDa on Western blots, consistent with native CaS from dorsal root ganglia. Both wild type (WT) and Gαq antisense knock-down (KD) cells responded to Ca(2+) and calindol, a positive allosteric modulator of the CaS, with a transient increase in intracellular Ca(2+) concentration ([Ca(2+)]i), which was larger in the Gαq KD cells.

Role of human pregnane X receptor in high fat diet-induced obesity in pre-menopausal female mice.

Obesity is a complex metabolic disorder that is more prevalent among women. Until now, the only relevant rodent models of diet-induced obesity were via the use of ovariectomized ("postmenopausal") females. However, recent reports suggest that the xenobiotic nuclear receptor pregnane X receptor (PXR) may contribute to obesity.

Role of pregnane X receptor in obesity and glucose homeostasis in male mice.

Clinical obesity is a complex metabolic disorder affecting one in three adults. Recent reports suggest that pregnane X receptor (PXR), a xenobiotic nuclear receptor important for defense against toxic agents and for eliminating drugs and other xenobiotics, may be involved in obesity. Noting differences in ligand specificities between human and mouse PXRs, the role of PXR in high fat diet (HFD)-induced obesity was examined using male PXR-humanized (hPXR) transgenic and PXR-knock-out (PXR-KO) mice in comparison to wild-type (WT) mice.