Both receptors bind agonist, but with different patterns of agonist recognition – particularly in the nature of the interactions between aromatic residues and the agonist quaternary amine functional

group. By comparing alpha 4 beta 2 and Torpedo receptors, we begin to delineate their structural similarities and differences. (C) 2011 Elsevier Inc. All rights reserved.”
“The calcium-sensing receptor (CaR) elicits oscillatory Ca-i(2+) mobilization associated with dynamic, inhibitory protein kinase C-mediated phosphorylation of CaRT888. While modest CaR stimulation elicits Ca-i(2+) PF 00299804 oscillations, greater stimulation either increases oscillation frequency or elicits sustained responses by an unknown mechanism. Here, moderate CaR stimulation (2.5 mM Ca-o(2+), 10 min) increased CaRT888 phosphorylation (160 kDa mature receptor) 5-fold in CaR stably transfected HEK-293 cells, whereas 3-5 mM Ca-o(2+) treatments were without

apparent effect. Treatment BMS-777607 clinical trial with 2 mM Ca-o(2+) caused sustained CaRT888 phosphorylation (>= 20 min) and oscillatory Ca-i(2+) mobilization. However, 5 mM Ca-o(2+) increased CaRT888 phosphorylation only briefly while eliciting sustained Ca-i(2+) mobilization, suggesting that greater CaR activation induces rapid CaRT888 dephosphorylation, thus permitting sustained Ca-i(2+) responses. Indeed, 5 mM Ca-o(2+) stimulated protein phosphatase 2A activity and induced CaRT888 dephosphorylation following acute phorbol ester pretreatment, the latter effect being mimicked by CaR-positive allosteric modulators (NPS-R467 and L-Phe). Finally, the phosphatase inhibitor calyculin-A reversed CaR-induced inhibition of parathyroid hormone secretion from bovine parathyroid slices and normal human parathyroid cells, demonstrating the physiological importance of phosphorylation

status on parathyroid function. Therefore, high Ca-o(2+)-stimulated protein kinase C acts in concert with high Ca-o(2+)- induced phosphatase activity to generate and maintain CaR-induced Ca-i(2+) oscillations via the dynamic phosphorylation and dephosphorylation of CaRT888.”
“Pituitary adenylate cyclase-activating Nepicastat chemical structure polypeptide (PACAP) is a peptidergic neurotransmitter that is highly expressed in the nervous system. We have previously reported that a central injection of PACAP leads to changes in the autonomic nervous system tones including sympathetic excitation and parasympathetic inhibition. An anatomical study revealed that melanocortin and PACAP are colocalized in some hypothalamic nuclei. Here, we investigated the possible role of the melanocortin system in autonomic control by PACAP using SHU9119, an antagonist of the melanocortin receptors (MC3-R/MC4-R).