A5083360421- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Pharmacological Receptor Mechanisms and Effects
- Pain Mechanisms and Treatments
- Neurotransmitter Receptor Influence on Behavior
- Ion channel regulation and function
- Neuroendocrine regulation and behavior
- Stress Responses and Cortisol
- Memory and Neural Mechanisms
- Cancer, Stress, Anesthesia, and Immune Response
- Pharmacological Effects and Assays
- Neuroinflammation and Neurodegeneration Mechanisms
- Photoreceptor and optogenetics research
- Lipid Membrane Structure and Behavior
- Nerve injury and regeneration
- Protein Kinase Regulation and GTPase Signaling
- Nicotinic Acetylcholine Receptors Study
- Adipose Tissue and Metabolism
- Chemokine receptors and signaling
- Epilepsy research and treatment
- Hypothalamic control of reproductive hormones
- Treatment of Major Depression
- Tryptophan and brain disorders
- Anesthesia and Pain Management
University of Washington
2014-2024
Seattle University
1991-2024
Institute of Pharmacology
2012-2018
University of Bristol
2013-2015
University of Bath
2015
University of California, Los Angeles
2012-2013
University of California, San Francisco
2013
Oregon Health & Science University
2013
University Hospital Magdeburg
2013
Friedrich Schiller University Jena
2013
In the guinea pig ileum myenteric plexus—longitudinal muscle preparation, dynorphin-(1—13) and prototypical κ agonist ethylketocyclazocine had equally poor sensitivity to naloxone antagonism showed selective cross protection in receptor inactivation experiments with alkylating antagonist β-chlornaltrexamine. binding assays membranes from brain, amide were more potent displacing tritium-labeled than typical μ δ opioid ligands. two preparations studied, dynorphin appears be same as receptor.
Kisspeptin is encoded by the Kiss1 gene, and kisspeptin signaling plays a critical role in reproduction. In rodents, neurons arcuate nucleus (Arc) provide tonic drive to gonadotropin-releasing hormone (GnRH) neurons, which turn supports basal luteinizing (LH) secretion. Our objectives were determine whether preprodynorphin ( Dyn ) neurokinin B NKB are coexpressed mouse evaluate its physiological significance. Using situ hybridization, we found that Arc of female mice not only express genes...
Stress is a complex human experience having both positive and negative motivational properties. When chronic uncontrollable, the adverse effects of stress on health are considerable yet poorly understood. Here, we report that dysphoric properties encoded by endogenous opioid peptide dynorphin acting specific stress-related neuronal circuits. Using different forms presumed to evoke dysphoria in mice, found repeated forced swim inescapable footshock produced aversive behaviors were blocked...
Previous studies have demonstrated that stress may increase prodynorphin gene expression, and κ opioid agonists suppress drug reward. Therefore, we tested the hypothesis stress-induced release of endogenous dynorphin mediate behavioral responses to oppose rewarding effects cocaine. C57Bl/6 mice subjected repeated forced swim testing (FST) using a modified Porsolt procedure at 30°C showed characteristic immobility response analgesia observed with tail withdrawal latency assay. Pretreatment...
The structural features responsible for the high potency and opiate receptor specificity of opioid peptide dynorphin in guinea pig ileum myenteric plexus were examined. Successive removal COOH-terminal amino acids from dynorphin-(1--13) demonstrated important contributions lysine-13, lysine-11, arginine-7 to potency. Removal NH2-terminal tyrosine abolished biologic activity. Several other modifications shown affect potency: substitution D-alanine glycine-2 reduced potencies amide, -(1--11),...
Synaptic vesicle protein 2 (SV2) is a membrane glycoprotein common to all synaptic and endocrine vesicles. Unlike many proteins involved in exocytosis, SV2 has no homolog yeast, indicating that it performs function unique secretion higher eukaryotes. Although the structure interactions of suggest multiple possible functions, its role events remains unknown. To explore an vivo context, we generated mice do not express primary isoform, SV2A, by using targeted gene disruption. Animals...
The murine Ca(2+)-stimulated adenylyl cyclase (type I) (EC 4.6.1.1), which is expressed predominantly in brain, was inactivated by targeted mutagenesis. activity reduced 40-60% the hippocampus, neocortex, and cerebellum. Long-term potentiation CA1 region of hippocampus from mutants perturbed relative to controls. Both initial slope maximum extent changes synaptic response were reduced. Although mutant mice learned find a hidden platform Morris water task normally, they did not display...
Although stress has profound effects on motivated behavior, the underlying mechanisms responsible are incompletely understood. In this study we elucidate a functional pathway in mouse brain that encodes aversive of and mediates stress-induced reinstatement cocaine place preference (CPP). Activation dynorphin/kappa opioid receptor (KOR) system by either repeated or agonist produces conditioned aversion (CPA). Because KOR inhibition dopamine release mesolimbic been proposed to mediate...
The endogenous dynorphin-κ opioid receptor (KOR) system encodes the dysphoric component of stress response and controls risk depression-like addiction behaviors; however, molecular neural circuit mechanisms are not understood. In this study, we report that KOR activation p38α MAPK in ventral tegmental (VTA) dopaminergic neurons was required for conditioned place aversion (CPA) mice. Conditional genetic deletion floxed or by Cre recombinase expression blocked to agonist U50,488. Selective...
Activity of several ion channels is controlled by heterotrimeric GTP-binding proteins (G proteins) via a membrane-delimited pathway that does not involve cytoplasmic intermediates. The best studied example the K+ channel activated muscarinic agonists in atrium, which plays crucial role regulating heartbeat. To enable studies molecular mechanisms activation, this channel, denoted KGA, was cloned from rat atrium cDNA library functional coupling to coexpressed serotonin type 1A receptors...
The molecular mechanisms mediating stress-induced dysphoria in humans and conditioned place aversion rodents are unknown. Here, we show that repeated swim stress caused activation of both κ-opioid receptor (KOR) p38 mitogen-activated protein kinase (MAPK) coexpressed GABAergic neurons the nucleus accumbens, cortex, hippocampus. Sites were visualized using phosphoselective antibodies against activated κ receptors (KOR-P) phospho-p38 MAPK. Surprisingly, increase P-p38-IR by swim-stress...
Desensitization of cannabinoid receptor signaling by a G-protein coupled kinase (GRK) was examined using the Xenopus oocyte expression system. Application CB1 agonist, WIN 55,212-2, evoked concentration-dependent increase in K + conductance (K ir 3) oocytes coexpressing rat with G-protein-gated, inwardly rectifying channels 3.1 and 3.4. slight during continuous agonist application absence GRK arrestin. However, coexpression GRK3 β-arrestin 2 (β-arr2) caused profound homologous...
AtT-20 cells expressing the wild-type kappa opioid receptor (KOR) increased phospho-p38 MAPK following treatment with agonist U50,488. The increase was blocked by antagonist norbinaltorphimine and not evident in untransfected cells. In contrast, U50,488 of KOR having alanine substituted for serine-369 (KSA) did phospho-p38. Phosphorylation serine 369 carboxyl terminus G-protein kinase 3 (GRK3) previously shown to be required desensitization, results suggest that p38 activation may require...