Activation characteristics of transient receptor potential ankyrin 1 and its role in nociception.

Transient receptor potential (TRP) ankyrin 1 (TRPA1) is a Ca(2+)-permeant, nonselective cationic channel. It is predominantly expressed in the C afferent sensory nerve fibers of trigeminal and dorsal root ganglion neurons and is highly coexpressed with the nociceptive ion channel transient receptor potential vanilloid 1 (TRPV1). Several physical and chemical stimuli have been shown to activate the channel.

Zinc Finger Nucleases: A new era for transgenic animals.

The rational engineering of eukaryotic genomes would facilitate the study of heritable changes in gene expression and offer enormous potential across basic research, drug-discovery, bioproduction and therapeutic development. A significant advancement toward this objective was achieved with the advent of a novel technology that enables high-frequency and high-fidelity genome editing via the application of custom designed zinc finger nucleases (ZFNs). A ZFN is a chimeric protein that consists of the non-specific endonuclease domain of FokI fused to a DNA-binding domain composed of an engineered zinc-finger motif.

Nociceptors in cardiovascular functions: complex interplay as a result of cyclooxygenase inhibition.

Prostaglandins (PGs) are requisite components of inflammatory pain as indicated by the efficacy of cyclooxygenase 1/2 (COX1/2) inhibitors. PGs do not activate nociceptive ion channels directly, but sensitize them by downstream mechanisms linked to G-protein coupled receptors. Antiinflammatory effects are purported to arise from inhibition of synthesis and/or release of proinflammatory agents.

Downregulation of transient receptor potential melastatin 8 by protein kinase C-mediated dephosphorylation.

Transient receptor potential melastatin 8 (TRPM8) and transient receptor potential vanilloid 1 (TRPV1) are ion channels that detect cold and hot sensations, respectively. Their activation depolarizes the peripheral nerve terminals resulting in action potentials that propagate to brain via the spinal cord. These receptors also play a significant role in synaptic transmission between dorsal root ganglion (DRG) and dorsal horn (DH) neurons.

Pontine reticular formation neurons are implicated in the neuronal network for generalized clonic seizures which is intensified by audiogenic kindling.

The caudal pontine reticular formation nucleus (cPRF) is implicated in seizure propagation to the spinal cord in several forms of generalized convulsive seizures, including audiogenic seizures (AGS). Focal microinjection studies implicate cPRF as a requisite neuronal network site subserving generalized AGS in the moderate severity substrain of genetically epilepsy-prone rats (GEPR-3s). AGS in GEPR-3s culminate in generalized clonus, but daily repetition of AGS (AGS kindling) results in an additional seizure behavior, facial and forelimb (F and F) clonus, not seen prior to kindling.

Activation of transient receptor potential vanilloid 1 (TRPV1) by resiniferatoxin.

Transient receptor potential vanilloid 1 (TRPV1) is a Ca(2+) permeable non-selective cation channel activated by physical and chemical stimuli. Resiniferatoxin (RTX), an ultrapotent agonist of TRPV1, is under investigation for treatment of urinary bladder hyper-reflexia and chronic pain conditions. Here, we have determined the characteristics of RTX-induced responses in cells expressing native and cloned rat TRPV1.

Evidence for the perirhinal cortex as a requisite component in the seizure network following seizure repetition in an inherited form of generalized clonic seizures.

Perirhinal cortex (PRh) is strongly implicated in neuronal networks subserving forebrain-driven partial onset seizures, but whether PRh plays a role in generalized onset seizures is unclear. The moderate seizure severity substrain of genetically epilepsy-prone rats (GEPR-3s) exhibits generalized onset clonic audiogenic seizures (AGS), but following repetitive AGS (AGS kindling), an additional behavior, facial and forelimb (F&F) clonus emerges immediately following generalized clonus. F&F clonus is thought to be driven from forebrain structures.

Neurons in the amygdala play an important role in the neuronal network mediating a clonic form of audiogenic seizures both before and after audiogenic kindling.

Previous studies showed that neuronal network nuclei for behaviorally different forms of audiogenic seizure (AGS) exhibit similarities and important differences. The amygdala is involved differentially in tonic AGS as compared to clonic AGS networks. The role of the lateral amygdala (LAMG) undergoes major changes after AGS repetition (AGS kindling) in tonic forms of AGS.

Block of native and cloned vanilloid receptor 1 (TRPV1) by aminoglycoside antibiotics.

Vanilloid receptor 1 (TRPV1) is a Ca2+ permeable non-specific cation channel located at the peripheral nerve terminals and functions as a polymodal nociceptor. Neomycin, an aminoglycoside antibiotic induces analgesia in various animal models. However, the mechanism of action of neomycin has not been fully understood.

Direct interaction of adenosine with the TRPV1 channel protein.

Vanilloid receptor 1 (TRPV1), a nonspecific cation channel expressed primarily in small sensory neurons, mediates inflammatory thermal pain sensation. The function and expression of TRPV1 are enhanced during inflammation and certain neuropathies, leading to sustained hyperalgesia. Activation of TRPV1 in the spinal cord and periphery promotes release of adenosine, which produces analgesia by activating A(1) and A(2A) adenosine receptor (AR) on central and peripheral neurons.

Enhancement of potency and efficacy of NADA by PKC-mediated phosphorylation of vanilloid receptor.

The search for an endogenous ligand for the vanilloid receptor (VR or TRPV1) has led to the identification of N-arachidonyl dopamine (NADA). This study investigates the role of protein kinase C (PKC)-mediated phosphorylation on NADA-induced membrane currents in Xenopus oocytes heterologously expressing TRPV1 and in dorsal root ganglion (DRG) neurons. In basal state, current induced by 10 microM NADA is 5-10% of the current induced by 1 microM capsaicin or protons at pH 5.

Identification of the requisite brain sites in the neuronal network subserving generalized clonic audiogenic seizures.

Comparative studies of neuronal networks that subserve convulsions in closely-related epilepsy models are revealing instructive data about the pathophysiological mechanisms that govern these networks. Studies of audiogenic seizures (AGS) in genetically epilepsy-prone rats (GEPRs) and related forms of AGS demonstrate important network similarities and differences. Two substrains of GEPRs exist, GEPR-9s, exhibiting tonic AGS, and GEPR-3s, exhibiting clonic AGS.