A5036928003- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Sleep and Wakefulness Research
- Regulation of Appetite and Obesity
- Hypothalamic control of reproductive hormones
- Chemical Synthesis and Analysis
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Neuroendocrine regulation and behavior
- Circadian rhythm and melatonin
- Pain Mechanisms and Treatments
- Neurobiology and Insect Physiology Research
- Pharmacological Receptor Mechanisms and Effects
- Neuroscience and Neuropharmacology Research
- Stress Responses and Cortisol
- Biochemical effects in animals
- Sleep and related disorders
- Biochemical Analysis and Sensing Techniques
- Mass Spectrometry Techniques and Applications
- Pharmacological Effects and Assays
- Memory and Neural Mechanisms
- Olfactory and Sensory Function Studies
- Cancer, Stress, Anesthesia, and Immune Response
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Monoclonal and Polyclonal Antibodies Research
Jena University Hospital
2017-2024
Friedrich Schiller University Jena
2017-2024
University Hospital Münster
2017-2021
University of Münster
2017-2021
University of California, Irvine
2008-2019
Pharmaceutical Biotechnology (Czechia)
2011
University of Ferrara
2003-2009
Istituto di Chimica Biomolecolare
2007
Universität Hamburg
1990-2000
Roche (Switzerland)
1995-1999
A heptadecapeptide was identified and purified from porcine brain tissue as a ligand for an orphan heterotrimeric GTP- binding protein (G protein)- coupled receptor (LC132) that is similar in sequence to opioid receptors. This peptide, orphanin FQ, has primary structure reminiscent of peptides. Nanomolar concentrations FQ inhibited forskolin-stimulated adenylyl cyclase activity cells transfected with LC132. inhibitory not affected by the addition ligands, nor did peptide activate Orphanin...
Orphanin FQ (OFQ) is the endogenous agonist of opioid receptor-like receptor (ORL-1). It and its precursor, prepro-OFQ, exhibit structural features suggestive peptides. A cDNA encoding OFQ precursor sequence in rat recently has been cloned, authors generated a polyclonal antibody directed against peptide. In present study, used situ hybridization immunohistochemistry to examine distribution peptide mRNA central nervous system adult rat. immunoreactivity prepro-OFQ expression correlated...
Orphanin FQ (OFQ, Nociceptin) is a recently discovered 17-amino acid neuropeptide that structurally related to the opioid peptides but does not bind receptors. OFQ has been proposed act as an anti-opioid peptide, its widespread sites of action in brain suggest it may have more general functions. Here we show plays important role higher functions because can anxiolytic attenuate behavioral inhibition animals acutely exposed stressful/anxiogenic environmental conditions. anxiolytic-like...
The recently discovered neuropeptide orphanin FQ (OFQ), and its opioid receptor-like (ORL1) receptor, exhibit structural features suggestive of the micro, kappa, delta systems. anatomic distribution OFQ immunoreactivity mRNA expression has been reported recently. In present analysis, we compare receptor with that binding at ORL1 in adult rat central nervous system (CNS). By using vitro autoradiography (125)I-[(14)Tyr]-OFQ as radioligand, was analyzed throughout CNS. Orphanin sites were...
Abstract Neuropeptide S (NPS) and its receptor (NPSR) constitute a novel neuropeptide system that is involved in regulating arousal anxiety. The NPS precursor mRNA highly expressed previously undescribed group of neurons located between the locus coeruleus (LC) Barrington's nucleus. We report here majority NPS‐expressing LC area principal sensory trigeminal nucleus are glutamatergic neurons, whereas many NPS‐positive lateral parabrachial coexpress corticotropin‐releasing factor (CRF). In...
The heptadecapeptide orphanin FQ (OFQ) is a recently discovered neuropeptide that exhibits structural features reminiscent of the opioid peptides and an endogenous ligand to G protein-coupled receptor sequentially related receptors. We have cloned both human rat cDNAs encoding OFQ precursor proteins, investigate whether sequence relationships existing between systems are also found at polypeptide level, in particular would encode several bioactive as do precursors, study regional...
The neuropeptide orphanin FQ (also known as nociceptin; OFQ/N) has been implicated in modulating stress-related behavior. OFQ/N was demonstrated to reverse stress-induced analgesia and possess anxiolytic-like activity after central administration. To further study physiological functions of OFQ/N, we have generated OFQ/N-deficient mice by targeted disruption the gene. Homozygous display increased anxiety-like behavior when exposed a novel threatening environment. OFQ/N-null show elevated...
We have recently shown that Neuropeptide S (NPS) can promote arousal and induce anxiolytic-like effects after central administration in rodents. Another study reported a number of natural polymorphisms the human NPS receptor gene. Some these were associated with increased risk asthma possibly other forms atopic diseases, but physiological consequences mutations remain unclear. One produces an Asn-Ile exchange first extracellular loop protein, C-terminal splice variant was found overexpressed...
The heptadecapeptide orphanin FQ (OFQ) is an endogenous ligand to opioid-like G protein-coupled receptor. Although the primary structure of OFQ exhibits some similarity opioid peptides, not recognized by receptors nor does receptor bind ligands. In order investigate structural determinants this ligand/receptor selectivity, we conducted a systematic structure-activity study on characterize which sites molecule are important for activation. Alanine- and D-amino acid-scanning mutagenesis...
The cysteinyl leukotrienes (CysLTs) are potent biological mediators in the pathophysiology of inflammatory diseases, particular airway obstruction asthma. Pharmacological studies have suggested existence at least two types CysLT receptors, designated CysLT<sub>1</sub> and CysLT<sub>2</sub>. CysLT<sub>1</sub>receptor has been cloned recently. Here we report molecular cloning, expression, localization, functional characterization a human G protein-coupled receptor that expected characteristics...
Orphanin FQ (OFQ) has recently been reported to be an endogenous ligand for the opioid-like LC132 receptor. The effect of OFQ on high voltage-gated calcium channels (VGCCs) was examined in freshly dissociated rat pyramidal neurons using whole-cell configuration patch-clamp technique. High-threshold Ba2+ currents were reversibly inhibited by OFQ. depression associated with a slowed rate activation and change I-V relationship at step potentials higher than +30 mV. In concentration-response...
Neuropeptide S (NPS) is the endogenous ligand for GPR154, now referred to as neuropeptide receptor (NPSR). Physiologically, NPS has been characterized a modulator of arousal and shown produce anxiolytic-like effects in rodents. Neuroanatomical analysis rat revealed that precursor mRNA strongly expressed brainstem only three distinct regions: locus coeruleus area, principal sensory trigeminal nucleus, lateral parabrachial nucleus. NPSR expression widely distributed, with strongest olfactory...
The opioid-like neuropeptide nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) are expressed in the substantia nigra (SN), a brain area containing dopamine neurons that degenerate Parkinson's disease. Endogenous N/OFQ facilitates nigral glutamate release inhibits nigrostriatal transmission motor behavior. Here, we present evidence suggesting endogenous may contribute to Pharmacological blockade of SN N/OFQ-NOP system attenuated parkinsonian-like akinesia/hypokinesia 6-hydroxydopamine...
Neuropeptide S (NPS) has been shown to modulate arousal, sleep wakefulness, anxiety-like behavior, and feeding after central administration of the peptide agonist mice or rats. We report here chemical synthesis pharmacological characterization SHA 66 (3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-<i>a</i>]pyrazine-7-carboxylic acid benzylamide) 68 4-fluoro-benzylamide), two closely related bicyclic piperazines with antagonistic properties at NPS receptor (NPSR). The compounds block NPS-induced...
Strict pharmacological selectivity in families of structurally related ligands and receptors may result from a key process evolution aiming at increasing diversity neurotransmission. An intriguing example such exclusive specificity can be found the newly discovered orphanin FQ (OFQ) system when it is compared with opioid system. Both OFQ its receptor share high degree sequence similarity to peptides their corresponding receptors, respectively. However, does not activate nor do elicit...