A5060173368- Calcium signaling and nucleotide metabolism
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Regulation of Appetite and Obesity
- Estrogen and related hormone effects
- Ion Channels and Receptors
- Hormonal Regulation and Hypertension
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Sleep and Wakefulness Research
- Pharmacological Receptor Mechanisms and Effects
- Neuroendocrine regulation and behavior
- Apelin-related biomedical research
- Barrier Structure and Function Studies
- Neuroscience of respiration and sleep
- Cellular transport and secretion
- Ion channel regulation and function
- Adenosine and Purinergic Signaling
- Pain Mechanisms and Treatments
- Hypothalamic control of reproductive hormones
- Piperaceae Chemical and Biological Studies
- Cannabis and Cannabinoid Research
- HIV Research and Treatment
- Stress Responses and Cortisol
- Menopause: Health Impacts and Treatments
Jefferson College
2015-2024
Thomas Jefferson University
2014-2024
Jefferson College of Health Sciences
2015-2024
Temple University
2005-2015
Balfour Beatty (United Kingdom)
2013
Yokogawa Electric (Japan)
2013
Agrobioinstitute
2012
Jensen Hughes (United States)
2011
Baoshan College
2010
New Mexico Cancer Center
2009
The G protein-coupled receptor 30 (GPR 30) has been identified as the non-genomic estrogen receptor, and G-1, specific ligand for GPR30. With use of a polyclonal antiserum directed against human C-terminus GPR30, immunohistochemical studies revealed GPR30-immunoreactivity (irGPR30) in brain adult male non-pregnant female rats. A high density irGPR30 was noted Islands Calleja striatum. In hypothalamus, detected paraventricular nucleus supraoptic nucleus. anterior posterior pituitary contained...
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a widespread and potent calcium-mobilizing messenger that highly unusual in activating calcium channels located on acidic stores. However, the molecular identity of target protein unclear. In this study, we show previously uncharacterized human two-pore (TPC1 TPC2) are endolysosomal proteins, NAADP-mediated signals enhanced by overexpression TPC1 attenuated after knockdown TPC1, mutation single conserved residue within putative pore...
We found that the selective stimulation of intracellular, transmembrane G protein–coupled estrogen receptor (GPER), also known as GPR30, acutely lowers blood pressure after infusion in normotensive rats and dilates both rodent human arterial vessels. Stimulation GPER blocks vasoconstrictor-induced changes intracellular calcium concentrations vascular tone, well serum-stimulated cell proliferation smooth muscle cells. Deletion gene mice abrogates effects activation is associated with visceral...
Nesfatin-1 is a recently identified satiety molecule detectable in neurons of the hypothalamus and nucleus solitary tract (NTS). Immunohistochemical studies revealed nesfatin-1-immunoreactive (irNEF) cells Edinger-Westphal nucleus, dorsal motor vagus, caudal raphe nuclei rats, addition to NTS reported initial study. Double-labeling immunohistochemistry showed that irNEF were vasopressin or oxytocin positive paraventricular supraoptic nucleus; cocaine-amphetamine-regulated transcript tyrosine...
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a ubiquitous messenger proposed to stimulate Ca(2+) release from acidic organelles via two-pore channels (TPCs). It has been difficult resolve this trigger event its amplification endoplasmic reticulum stores, fuelling speculation that archetypal intracellular are the primary targets of NAADP. Here, we redirect TPC2 lysosomes plasma membrane and show NAADP evokes influx independent ryanodine receptors it activates Ca(2+)-permeable...
Two-pore channels (TPCs) are endo-lysosomal ion implicated in Ca2+ signalling from acidic organelles. The relevance of these ubiquitous proteins for human disease however is unclear. Here we report that lysosomes enlarged and aggregated fibroblasts Parkinson patients with the common G2019S mutation LRRK2. Defects were corrected by molecular silencing TPC2, pharmacological inhibition TPC regulators (Rab7, NAADP, PI(3,5)P2) buffering local increases. NAADP-evoked signals exaggerated diseased...
Background and Purpose GPR 18 is a candidate cannabinoid receptor, but its classification as such controversial. The rationale of the study presented herein was to consider effects N ‐arachidonoyl glycine ( NAG ly) cannabinoids via differential G ‐protein coupled pathways, in addition β‐arrestin signalling. Cellular localization receptors also examined. Experimental Approach Calcium mobilization ERK 1/2 phosphorylation were quantified cell line stably expressing HEK 293/ cells). In addition,...
Molecular modeling, pharmacology, and comparative genomics reveal secrets of ion channel evolution.
The two recently isolated hypothalamic peptides orexin A and B, also known as hypocretin 1 2, are reported to be important signaling molecules in feeding sleep/wakefulness. Orexin-containing neurons the lateral hypothalamus project numerous areas of rat brain spinal cord including intermediolateral cell column (IML) thoracolumbar cord. An vivo vitro study was undertaken evaluate hypothesis that orexins, acting on sympathetic preganglionic (SPNs) cord, increase outflow. First, (0.3, 1, 10...
Abstract Metastin, the gene product of metastasis suppressor KiSS‐1, is endogenous ligand for G‐protein‐coupled receptor GPR54 (or AXOR12, or OT7T175). The expression KiSS‐1 and peptide distribution metastin were studied in rat central nervous system by reverse transcriptase‐polymerase chain reaction, Western blotting, immunohistochemical methods. was higher hypothalamus than brainstem spinal cord. In brain, metastin‐like immunoreactivity (irMT) found mainly three groups cells: dorsomedial...
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent and widespread calcium-mobilizing messenger, the properties of which have been most extensively described in sea urchin eggs. The molecular basis for calcium release by NAADP, however, not clear subject to controversy. Recent studies provided evidence that members two-pore channel (TPC) family mammals are long sought after target channels NAADP. Here, we show TPC3 gene, has yet be functionally characterized, present throughout...
Recent studies have demonstrated that the majority of endogenous cannabinoid type 1 (CB1) receptors do not reach cell surface but are instead associated with endosomal and lysosomal compartments. Using calcium imaging intracellular microinjection in CB1 receptor-transfected HEK293 cells NG108-15 neuroblastoma × glioma cells, we provide evidence anandamide acting on increases concentration when administered intracellularly extracellularly. The calcium-mobilizing effect was dose-dependent...
Sigma-1 receptors (Sig-1Rs) are integral ER membrane proteins. They bind diverse ligands, including psychoactive drugs, and regulate many signaling proteins, the inositol 1,4,5-trisphosphate (IP3Rs) that release Ca2+ from ER. The endogenous ligands of Sig-1Rs unknown. Phospholipase D (PLD) cleaves phosphatidylcholine to choline phosphatidic acid (PA), with PA assumed mediate all downstream signaling. We show is also an intracellular messenger. Choline binds Sig-1Rs, it mimics other Sig-1R...
Lysosomes and the endoplasmic reticulum (ER) are Ca2+ stores mobilized by second messengers NAADP IP3, respectively. Here, we establish signals between two sources as fundamental building blocks that couple local release to global changes in Ca2+. Cell-wide evoked activation of endogenous NAADP-sensitive channels on lysosomes comprise both components exhibit a major dependence ER despite their lysosomal origin. Knockout IP3 receptor delays these signals, whereas expression TPC2 accelerates...
Obestatin, a 23 amino acid peptide recently isolated from the rat stomach, is encoded by same gene that encodes ghrelin. With use of an antiserum directed against mouse/rat obestatin, obestatin immunoreactivity (irOBS) was detected in cells gastric mucosa, myenteric plexus, and Leydig testis Sprague-Dawley rats. Double labeling plexus with choline acetyltransferase (ChAT) revealed nearly all irOBS neurons were ChAT positive vice versa. For comparative purposes, ganglion cells, shown to be...
Ca(2+) regulates a spectrum of cellular processes including many aspects neuronal function. Ca(2+)-sensitive events such as neurite extension and axonal guidance are driven by signals that precisely organized in both time space. These complex cues result from influx across the plasma membrane mobilization intracellular stores. In present study, using rat cortical neurons, we have examined effects novel Ca(2+)-mobilizing messenger nicotinic acid adenine dinucleotide phosphate (NAADP) on...
Cells possess several Ca2+-mobilizing messengers, which couple stimulation at the cell surface by a multitude of extracellular cues to regulation intracellular Ca2+-sensitive targets. Recent studies suggest that agonists differentially select from this molecular palette generate their characteristic Ca2+ signals but it is still unclear whether different messengers mediate functions or they act in redundant fashion. In study, we compared effects nicotinic acid adenine dinucleotide phosphate...
The G protein-coupled receptor GPR30 has recently been identified as a nonnuclear estrogen receptor. Reverse transcriptase-polymerase chain reaction revealed expression of mRNA in varying quantities the rat spinal cord, dorsal root ganglia, nodose trigeminal hippocampus, brain stem, and hypothalamus. Immunohistochemical studies that used rabbit polyclonal antiserum against human C-terminus fine network GPR30-immunoreactive (irGPR30) cell processes superficial layers cord; some which extended...
The therapeutic and psychoactive properties of cannabinoids have long been recognized. type 2 receptor for (CB2) has emerged as an important target in several pathologies, it mediates beneficial effects while having little if any psychotropic activity. Difficulties associated with the development CB2-based agents related to its intricate pharmacology, including species specificity functional selectivity CB2-initiated responses. We postulated that a plasmalemmal or subcellular location may...
Emerging evidence indicates the involvement of GPR55 and its proposed endogenous ligand, lysophosphatidylinositol (LPI), in nociception, yet their role central pain processing has not been explored. Using Ca<sup>2+</sup> imaging, we show here that LPI elicits concentration-dependent GPR55-mediated increases intracellular levels dissociated rat periaqueductal gray (PAG) neurons, which express mRNA. This effect is mediated by release from endoplasmic reticulum via inositol 1,4,5-trisphosphate...
Accumulating evidence implicates nicotinic acid adenine dinucleotide phosphate (NAADP) in the control of Ca(2+)-dependent functions. Little, however, is known concerning its role vascular endothelium, a major regulator blood pressure. Here, we show that NAADP acetoxymethyl ester (NAADP-AM), cell-permeant analog, increases cytosolic Ca(2+) concentration aortic endothelial cells. We demonstrate these signals and those evoked by acetylcholine are blocked disrupting acidic organelles with...
Sigma-1 receptor (Sig-1R) is an intracellular chaperone protein with many ligands, located at the endoplasmic reticulum (ER). Binding of cocaine to Sig-1R has previously been found modulate endothelial functions. In present study, we show that dramatically inhibits store-operated Ca(2+) entry (SOCE), a influx mechanism promoted by depletion stores, in rat brain microvascular cells (RBMVEC). Using either shRNA or pharmacological inhibition unrelated antagonists BD-1063 and NE-100,...
Faster cellular effects of aldosterone incompatible with the genomic mediated by mineralocorticoid receptors have been proposed for 40 years but remained elusive. Recently, has shown to activate G protein-coupled oestrogen receptor (GPER) in vasculature. Our results indicate that activates GPER cardiac vagal neurons nucleus ambiguus leading an increase cytosolic Ca2+ concentration and depolarization; addition, vivo studies microinjection produces bradycardia conscious rats. In summary, our...