ATP-gated P2X3 receptors are mostly expressed by nociceptive sensory neurons and participate in transduction of pain signals. P2X3 receptors show a combination of fast desensitization onset and slow recovery. Moreover, even low nanomolar agonist concentrations unable to evoke a response, can induce desensitization via a phenomenon called "high affinity desensitization." We have also observed th...

Antigenic components were solubilized from a participate fraction of mouse lymphosarcoma 6C3HED at pH 9.0-9.5. Protein, lipid, and carbohydrate were present. Three measures of antigenicity were employed. Mouse cytotoxicity tests re vealed that the tumor fraction adsorbed a greater amount of rabbit antitumor antibody than did similar fractions of normal C3H mouse lymphoid tissues. In Schultz-Dal...

Fast IPSCs in the brain are predominantly caused by presynaptic release of GABA that activates GABA(A) receptor (GABA(A)R) channels. The IPSCs are shaped by the gating and desensitization properties of postsynaptic GABA(A)Rs. Specifically, fast desensitization has been suggested to decrease IPSC amplitude and to increase IPSC duration by slowing deactivation; however, the mechanisms underlying ...

Recently, with use of rat dorsal root ganglion (DRG) neurons we have been able to dissociate the binding affinities of vanilloids from their potencies to induce 45Ca uptake, which suggests the existence of distinct classes of the vanilloid receptor (). In the present study, we have demonstrated that the ultrapotent capsaicin analog resiniferatoxin (RTX) desensitized rat DRG neurons to the subse...

It has previously been shown that nitric oxide (NO) synthase is involved in the development of opioid tolerance. The aim of the present work was to study the effect of NO on μ-opioid receptor (MOR) desensitization. Furthermore, we explored the possible role of reactive oxygen species (ROS) in this effect. Single-unit extracellular and whole-cell patch-clamp recordings were performed on locus co...

The acid sensing ion channels (ASICs) are proton-gated, voltage-insensitive cation channels expressed throughout the nervous system. ASIC1a plays a role in learning, pain, and fear related behaviors. In addition, activation of ASIC1a during prolonged acidosis following cerebral ischemia induces neuronal death. ASICs undergo steady-state desensitization, a characteristic that limits ASIC1a activ...

Desensitization is a general property of ligand-gated ion channels. Because of a wide array of available subunit combinations, it generates different time constants for channel closure, thereby modulating the processing of information in the brain. Within the family of neuronal nicotinic acetylcholine receptors (nAChRs), alpha 3 beta 2 and alpha 3 beta 4 receptors display contrasting properties...

The intestinal immune system mounts inflammatory responses to pathogens but tolerates harmless commensal microbiota. Various mechanisms for pathogen/non-pathogen discrimination have been proposed but their general relevance for inflammation control is unclear. Here, we compared intestinal responses to pathogenic Salmonella and non-pathogenic E. coli. Both microbes entered intestinal Peyer's pat...

We studied the effects of protein kinase C (PKC) activation on endothelial cell surface expression and function of the proteolytically activated thrombin receptor 1 (PAR-1). Cell surface PAR-1 expression was assessed by immunofluorescence (using anti-PAR-1 monoclonal antibody), and receptor activation was assessed by measuring increases in cytosolic Ca2+ concentration in human dermal microvascu...

The classic type of transient receptor potential channel (TRPC) is a molecular candidate for Ca(2+)-permeable cation channel in mammalian cells. TRPC5 is desensitized rapidly after activation by G protein-coupled receptor. Herein we report our investigation into the desensitization of mTRPC5 and localization of the molecular determinants of this desensitization using mutagenesis. TRPC5 was init...