Biomedical subjects

S Florin

Publications and source records attributed to S Florin.

12 recordsLinked to original sources

PubMed2000

Autoradiographic localization of [3H]nociceptin binding sites in the rat brain.

The binding sites of nociceptin (also named orphanin FQ), the endogenous ligand of ORL1 (opiate receptor like 1), were localized in rat brain, using an autoradiographic procedure. High levels of binding were observed in the cingulate, retrosplenial, perirhinal, insular and occipital cortex, anterior and posteromedial cortical amygdaloid nuclei, basolateral amygdaloid nucleus, amygdaloid complex, posterior hippocampus, dorsal endopiriform, central medial thalamic, paraventricular, rhomboid thalamic, suprachiasmatic, ventromedial hypothalamic nuclei, mammillary complex, superficial gray layer of the superior colliculus, locus coeruleus, dorsal raphe nucleus. More moderate labelling was observed in the prefrontal, fronto-parietal, temporal, piriform cortex, dentate gyrus, anterior olfactory nucleus, olfactory tubercle, shell of nucleus accumbens, claustrum, lateral septum, laterodorsal thalamic, medial habenular, subthalamic, reuniens thalamic nuclei, subiculum, periaqueductal grey matter and pons. A lower binding site density was observed in the anterior and medial hippocampus, olfactory bulb, caudate putamen, the core of the nucleus accumbens, medial septum, ventrolateral, ventroposterolateral and mediodorsal thalamic nuclei, lateral and medial geniculate nuclei, hypothalamic area, substantia nigra, ventral tegmentum area and interpedoncular nucleus. A moderate and similar labelling was found in the dorsal and ventral horn of the spinal cord. No labelling was apparent in the corpus callosum. Thus, it appears that the ORL1 receptor is particularly abundant in the cerebral cortex, limbic system of the rat brain and some areas involved in pain perception.

Animals↗

PubMed2000

Synchrotron beam test with a photon-counting pixel detector.

Synchrotron beam measurements were performed with a single-photon-counting pixel detector to investigate the influence of threshold settings on charge sharing. Improvement of image homogeneity by adjusting the threshold of each pixel individually was demonstrated. With a flat-field correction, the homogeneity could be improved. A measurement of the point spread function is reported.

Journal Article↗

PubMed1999

Comparison of behavioural effects of NocII or NocIII, two related pronociceptin-derived peptides.

Prepronociceptin contains, in addition to nociceptin, other potentially excisable peptides which may have physiological significance. We have here considered NocII, a heptadecapeptide whose sequence lies immediately downstream of that of nociceptin in the precursor polypeptide, as well as NocIII which corresponds to NocII extended by a stretch of three arginine residues. When i.c.v.-administered in mice, NocII (10-10,000 ng) stimulated horizontal locomotor activity and decreased the latency to paw licking but neither to rearing nor escape jumping in the hot plate test (55 degrees C). When nociceptin (100 ng) and NocII (100 ng) were simultaneously intracerebroventricularly injected, each peptide produced its own effect without modifying the effect of the other. NocII was ineffective in the tail flick and writhing tests. NocIII (NocII-Arg-Arg-Arg) was inactive in all tests, even when assayed as long as 40 min following i.c.v. administration. The fact that NocII, but not its very close structural analogue NocII, is biologically active indicates that their may exist a specific receptor to NocII.

Amino Acid Sequence↗

PubMed1998

Nociceptin-induced apparent hyperalgesia in mice as a result of the prevention of opioid autoanalgesic mechanisms triggered by the stress of an intracerebroventricular injection.

The effects on nociperception of nociceptin/Orphanin FQ (noc/OFQ), the endogenous ligand of the ORL1 (opioid receptor like 1) receptor, have been evaluated in mice upon intracerebroventricular injection of 10 to 10,000 ng doses of the peptide. In the hot plate test (55 degrees C) the licking, rearing and jump latencies were significantly reduced by noc/OFQ (100-250 ng). Noc/OFQ (100-1000 ng) also reduced the latency to tail withdrawal in the tail flick test. In the formalin test (injection in a hind paw of a formalin solution), noc/OFQ (100 ng) increased significantly the duration of paw licking and/or biting at the earliest period of observation. In the writhing test, the number of writhes evoked by intraperitoneal administration of dilute acetic acid was not modified by noc/OFQ at doses in the range of 10-1000 ng, but was decreased by 10,000 ng. The reduction in jump latency in the hot plate test was observed even when mice were pretreated with morphine (2 mg/kg, s.c.). The analgesic effect of acetorphan (5 mg/kg, i.v.) was also reduced by nociceptin (100 ng); on the other hand the hyperalgesic effect of naloxone (4.5 mg/kg, s.c.) was not additive with that of nociceptin (100 ng). Comparing in various tests the nociceptive thresholds of uninjected mice to that of saline i.c.v. injected mice, it appeared that the latter injection induced an increase in these thresholds which was prevented by nociceptin. It is suggested that nociceptin displays hyperalgesic effects by preventing autoanalgesic (opioidergic) mechanisms triggered by the stress elicited by intracerebroventricular injection.

Analgesia↗

PubMed1998

[Cloning of prepronociceptin has led to the discovery of other biologically active peptides].

Among the opioid receptors family, the cloning of the mu, kappa and delta receptors was followed by that of another member, named ORL1 (Opiate Receptor Like 1). In spite of obvious homologies with the mu, kappa and delta receptors, ORL1 does not display a relevant affinity for the endogenous ligands of these former receptors (beta endorphin, enkephalins, dynorphin A...). This observation has prompted to search for an endogenous ligand of ORL1. A heptadecapeptide which fulfils this function, with a nanomolar affinity, has been found. It was named either nociceptin or orphanin FQ. It demonstrates, according either to the dose or to the route of administration, hyperalgesic, allodynic, antiopioidergic or even analgesic effects. It displays also many behavioural effects, modifying especially locomotion, exploratory behaviour, motivation, anxiety, memory, food intake. Nociceptin results from the cleavage of a large precursor protein, prepronociceptin (PPNOC). In this latter, nociceptin is flanked on its C-terminal region by another peptide which may be regarded either as a heptadecapeptide (NocII), or a bidecapeptide (NocIII) according to the inclusion or not of a fragment constituted by 3 arginine residues. Investigating the functions modulated by NocII, we observed that it stimulates locomotor activity of mice and shortens the forepaws licking latency in the hot plate test (55 degrees C); these effects are not shared by NocIII. The simultaneous administration of NocII and nociceptin resulted in animals put on the hot plate to the appearance of their respective effects, not modified by the presence of the other. A 41 amino acid peptide flanks nociceptin on its N-terminal region in PPNOC. It may be cleaved to generate a heptadecapeptide, named nocistatin on account of its antagonist effect on the hyperalgesia/allodynia induced by nociceptin. Thus, the discovery of ORL1 has led to that of nociceptin, that of its precursor PPNOC, and thereby to that of NocII/NocIII and nocistatin. The functions modulated by these peptides are being investigated whereas their receptors are yet unknown. These multiple targets allow to expect new strategies to modulate their functions.

Animals↗

PubMed1997

Autoradiographic localization of [3H]nociceptin binding sites from telencephalic to mesencephalic regions of the mouse brain.

The binding sites of [3H]nociceptin (also named Orphanin FQ), the endogenous ligand of the ORL1 (opiate receptor like 1) receptor, were localized in the central nervous system of the mouse using an autoradiographic procedure. A high density of binding sites was seen in the cerebral cortex, paraventricular nucleus of the thalamus, amygdaloid complex, suprachiasmatic nucleus, medial thalamus and medial geniculate nucleus. Moderate binding was observed in the nucleus accumbens, lateral septum, lateral thalamus, hippocampus, periaqueductal grey matter and pons. Finally, low levels of binding were seen in the striatum, olfactory tubercle, hypothalamus and substantia nigra. Thus, it appears that the ORL1 receptor is particularly abundant in the cerebral cortex and limbic system of the mouse brain.

Amygdala↗

PubMed1997

Orphan neuropeptide NocII, a putative pronociceptin maturation product, stimulates locomotion in mice.

NocII is a heptadecapeptide whose sequence lies immediately downstream of nociceptin, the newly discovered natural agonist of the ORL1 receptor, in pronociceptin, nociceptin's precursor polypeptide. Since the sequence of NocII is framed by putative convertase excision sites and it totally conserved across murine and human species, we have sought to determine whether this orphan neuropeptide might by physiologically significant, i.e. endowed with central biological activity in vivo. Intracerebroventricular administration of 10 and 100 ng of NocII increased locomotion in mice. However, unlike nociceptin, which stimulates both the horizontal and vertical (rearing) components of locomotion, NocII affected only the horizontal component. The motor stimulant action of NocII appears to depend largely on dopamine transmission since it is totally reversed by the D1 or the D2 dopamine receptor antagonists SCH 23390 and haloperidol. NocII does not modify the number of explored holes in the hole board test, indicating that, unlike nociceptin, the orphan peptide does not affect exploratory behavior in mice.

Amino Acid Sequence↗

PubMed1996

Nociceptin stimulates locomotion and exploratory behaviour in mice.

The recently characterized heptadecapeptide nociceptin, the endogenous agonist of the orphan opioid receptor-like 1 (ORL1 receptor), has been tested for its effects on locomotion and exploratory behaviour in mice. I.c.v. administration of as little as 10 ng of nociceptin/animal stimulated locomotor activity. This effect was dose-dependent, increasing in intensity up to 100 ng and in duration for doses in the range of 1000-10000 ng. The stimulation of horizontal locomotion elicited by 100 ng nociceptin was accompanied by a stimulation of the vertical component of locomotion. These effects were not reversed by high doses (1.5 and 4.5 mg/kg s.c.) of the opioid receptor antagonist naloxone. Increasing doses of the dopamine D2 receptor antagonist haloperidol (0.1-0.5 mg/kg i.p.) as well as of the dopamine D1 receptor antagonist SCH 23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine hydrochloride] (0.0075-0.03 mg/kg s.c.) reversed this effect, suggesting that nociceptin exerts its motor-stimulant actions by increasing central dopaminergic transmission. Nociceptin was also found to increase the number of head dips in the hole-board test, indicating that the peptide stimulates exploratory behaviour.

Animals↗

PubMed1995

Effects of azapropazone on pain-related brain activity in human subjects.

1. The dose-related effects of azapropazone on (i) event-related and spontaneous EEG-activity and (ii) the subjects' pain ratings were investigated using an experimental human pain model based on both chemo-somatosensory event-related potentials (CSSERP) and subjects' pain ratings. 2. Healthy subjects (n = 20) participated in a placebo-controlled, randomized, double-blind, four-way cross-over study. Single doses of azapropazone (300 mg, 600 mg and 1200 mg) and placebo were administered intravenously. Each experiment consisted of five sessions (before and 1, 2, 4 and 8 h after administration of the medication). Each session lasted for approximately 40 min. In the first 20 min, pain was induced by short CO2-stimuli presented to the right nostril (phasic pain; interstimulus interval 30 s) and EEG was recorded from five positions. CSSERPs were obtained in response to painful CO2-stimuli. In the following 20 min period, tonic pain was induced by a constant stream of dry air introduced in the left nostril. Subjects rated the intensity of both phasic and tonic pain by means of a visual analogue scale. Additionally, a frequency analysis of the spontaneous EEG was performed. 3. Azapropazone reduced the pain-related CSSERP-amplitudes at frontal and parietal recording positions. This topographical pattern was observed in previous studies with opioids, while NSAIDs such as flurbiprofen and ketoprofen exerted effects at frontal and central positions. In contrast to other NSAIDs, administration of azapropazone resulted in a reduction of the frequency bands alpha 1, delta and theta of the spontaneous EEG. At the subjective level, analgesic effects of azapropazone were observed in the ratings of tonic pain. 4. Analgesic properties of azapropazone were demonstrated in man. The topographical pattern of the changes in the CSSERPs and the effects on EEG background activity suggest a central component of the analgesic action of azapropazone.

Adult↗

PubMed1989

Use of 19F NMR spectroscopy for measurement of cerebral blood flow: a comparative study using microspheres.

19F NMR was used to determine washout curves of an inert, diffusible gas (CHF3) from the cat brain. The cerebral blood flow was estimated from a bi- or tri-phasic fit to the deconvoluted wash-out curve, using the Kety-Schmidt approach. Cerebral blood flow values determined by 19F NMR show the expected responsiveness to alterations in Paco2, but are approximately 28% lower than cerebral blood flow values determined simultaneously by radioactive microsphere techniques. High concentrations of CHF3 have little effect on intracranial pressure, mean arterial blood pressure or Paco2, but cause small changes in the blood flow to certain regions of the brain. We conclude that 19F NMR techniques utilizing low concentrations of CHF3 have potential for the noninvasive measurement of cerebral blood flow.

Animals↗

PubMed1989

Cerebral blood flow and glucose metabolism in experimental brain edema.

The relationship between cerebral blood flow (CBF) and cerebral metabolic rate of glucose (CMRgl) in the white matter was studied in a plasma infusion model of vasogenic edema in cats. Local CBF, as determined by iodoantipyrine testing, was found to be significantly decreased in edematous white matter (mean +/- standard error of the mean: 17.3 +/- 1.5 ml/100 gm/min) when compared with CBF in the contralateral control white matter (24.8 +/- 1.8 ml/100 gm/min). When the values for edematous brain were corrected for dilution, however, the local CBF averaged 25.3 +/- 1.7 ml/100 gm/min, which was similar to the control value. Local CMRgl was found to be significantly increased in plasma-infused white matter (16.3 +/- 2.2 mumol/100 gm/min) compared with that in control white matter (10.7 +/- 1.3 mumol/100 gm/min). This difference remained, despite correction for dilution and recalculation of local CMRgl values based on altered kinetic constants found in edematous brain. A similar increase in local CMRgl was noted with saline-infusion edema. It is concluded that the increased tissue water level does not alter CBF, but does induce an increase in anaerobic metabolism.

Animals↗

PubMed1988

Iron deficiency in Bourke children.

A study of 121 Aboriginal and 91 non-Aboriginal children aged 6 years and under was carried out in Bourke during 6 months of 1986. These children were selected either because they were admitted to hospital and had an incidental blood test or were screened at various childcare and preschool facilities in the town. A haemoglobin level of below 100 g/l was found in 12.4% of Aboriginal children compared with only 3.3% of non-Aboriginal children. A mean corpuscular volume of less than 80 was found in 15.7% of Aboriginal children and 3.3% of non-Aboriginal children. Of the total sample, 17.4% of Aboriginal children and 6.6% of non-Aboriginal children had a serum ferritin level of less than 10 ng/ml. These markers of iron deficiency were associated with low weight and crowded living conditions in Aboriginal children. The prevalence of haemoglobin below 100 g/l among Aboriginal children under 5 years has fallen from 24.7% in 1971 to 14.1% in 1986.

Child↗