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F Cesselin

Publications and source records attributed to F Cesselin.

At least 73 records · Page 4Linked to original sources
PubMed1990

Cholecystokinin-like immunoreactivity in the dorsal horn of the rat spinal cord: an attempt to analyse contradictory results between immunocytochemistry and radioimmunoassay.

This study investigated the nature of the cholecystokinin-like immunoreactivity (CCKLI) in the dorsal horn of the rat spinal cord. Indeed, using the same antiserum, no variation of radioimmunoassayable CCKLI in the dorsal horn of rats treated neonatally with capsaicin could be seen, whereas the density of immunoreactive CCKLI fibres was greatly reduced in immunocytochemistry (IC). By comparing the technical conditions used in IC and radioimmunoassay (RIA), it could be concluded that the contradictory results obtained by the two techniques were very unlikely due to the fixation of the tissues, but rather to the concentration of the antiserum. First, CCKLI levels in extracts from fresh or 4% paraformaldehyde fixed tissues were not significantly different. Second, glomerular terminals, which are typical terminals of the fine primary afferents were immunoreactive at the surface of the block but unlabelled in its depth, where the concentration of antiserum might gradually reach a value closer to that used in radioimmunoassay. High pressure liquid chromatography analyses of acidic extracts of the dorsal part of the lumbar spinal cord of control rats revealed the presence, besides two major peaks coeluting with sulphated and non-sulphated CCK8, of two minor peaks '1' and '2' accounting for 23% of total CCKLI. Capsaicin treatment resulted in the disappearance of peak 2 and a marked reduction in the proportion of CCKLI in peak 1. Reported data suggested that the CCKLI material present in capsaicin-sensitive neurons, accounting for only about 10% of radioimmunoassayable CCKLI but for a much higher proportion of that detected in IC, was distinct from both genuine CCK and CGRP.

Animals↗
PubMed1990

Subcutaneous formalin induces a segmental release of Met-enkephalin-like material from the rat spinal cord.

The possible influence of a noxious chemical stimulus on the activity of spinal enkephalinergic neurones was examined by measuring the outflow of Met-enkephalin-like material (MELM) in CSF perifusates from the lumbar and cervico-trigeminal zones in halothane-anaesthetized rats. Following subcutaneous injection of 50 microliters of a 10% formalin solution in saline into the muzzle, MELM outflow increased at the cervico-trigeminal level but not at the lumbar level. Conversely, a significant enhancement in MELM outflow occurred at the lumbar but not at the cervico-trigeminal level when formalin was injected into a hind paw. In both cases, the increase in MELM release took place 5-10 min after the treatment and was of short duration (5-10 min). It is concluded that noxious chemical stimuli can induce a transient activation of enkephalinergic neurones within spinal zones receiving the nociceptive inputs. The marked differences in the characteristics of spinal MELM overflow due to noxious chemical, thermal and mechanical stimuli further support the notion that each type of nociceptive stimulus probably activates spinal enkephalinergic systems by triggering distinct neuronal mechanisms.

Animals↗
PubMed1990

Origin of some enkephalin-containing afferents to the ventro-medial region of the globus pallidus in the rat.

The retrograde transport of WGA-HRP adsorbed to colloidal gold was combined with the indirect immunoperoxidase technique to study the origin of enkephalin-containing afferents to the medial and ventral regions of the globus pallidus (GP). On the injected side, the nerve cell bodies labeled retrogradely or double labeled were numerous in the central nucleus of the amygdala (ACe), scattered in the bed nucleus stria terminalis (BNST) and few in the fundus striati. In the ACe, approximately 40% and 20% of the retrogradely labeled perikarya were found immunoreactive for Met-enkephalin and Leu-enkephalin, respectively, whereas they were only 30% and 15% in the BNST. It is concluded that the enkephalinergic afferents of the ventro-medial region of GP, which contains the basal nucleus of Meynert in the rat, are largely of limbic origin.

Amygdala↗
PubMed1990

Regional distribution of calcitonin gene-related peptide-, substance P-, cholecystokinin-, Met5-enkephalin-, and dynorphin A (1-8)-like materials in the spinal cord and dorsal root ganglia of adult rats: effects of dorsal rhizotomy and neonatal capsaicin.

Biochemical mapping of five different peptide-like materials--calcitonin gene-related peptide (CGRP), substance P (SP), Met5-enkephalin (ME), cholecystokinin (CCK), and dynorphin A (1-8) (DYN)--was conducted in the dorsal and ventral zones of the spinal cord at the cervical, thoracic, and lumbar levels in 3-month-old rats 10 days after unilateral dorsal rhizotomy at the cervical level (C4-T2) or after neonatal administration of capsaicin (50 mg/kg s.c.). In control rats, all peptide-like materials were more abundant in the dorsal than in the ventral zone all along the spinal cord. However, in both zones, absolute concentrations of CGRP, SP, ME, and CCK were significantly higher at the lumbar than at the cervical level. Rhizotomy-induced CGRP depletion (-85%) within the ipsilateral dorsal zone of the cervical cord was more pronounced than that due to neonatal capsaicin (-60%), a finding suggesting that this peptide is contained in both capsaicin-sensitive (mostly unmyelinated) and -insensitive (myelinated) primary afferent fibers. In contrast, similar depletions of SP (-50%) were observed after dorsal rhizotomy and neonatal capsaicin treatment, as expected from the presence of SP only in the capsaicin-sensitive small-diameter primary afferent fibers. Although the other three peptides remained unaffected all along the cord by either intervention, evidence for the existence of capsaicin-insensitive CCKergic primary afferent fibers could be inferred from the increased accumulation of CCK (together with SP and CGRP) in dorsal root ganglia ipsilateral to dorsal root sections.

Afferent Pathways↗
PubMed1989

Intrathecal porcine calcitonin enhances the release of [Met5]enkephalin-like material from the rat spinal cord.

Perfusion of the intrathecal space of halothane-anaesthetized rats with artificial cerebro-spinal fluid supplemented with porcine calcitonin (1-10 microM) produced a significant increase (+67-110%) in the spinal release of [Met5]enkephalin-like material. The effect of porcine calcitonin was markedly enhanced (+100%) in animals receiving a continuous i.v. infusion of the opioid antagonist naloxone (65 micrograms/kg per min). These data strongly suggest that the antinociceptive effect of intrathecal porcine calcitonin might involve a stimulatory action of the hormone on spinal enkephalinergic interneurones. In addition, presynaptic opioid autoreceptors probably control the activity of these neurones in the rat.

Animals↗
PubMed1989

Segmental release of Met-enkephalin-like material from the spinal cord of rats, elicited by noxious thermal stimuli.

In order to investigate possible changes induced by noxious thermal stimuli in the activity of enkephalinergic neurones at various levels of the spinal cord, either the whole cord, the cervicotrigeminal area or the lumbar area were perifused with artificial CSF at a rate of 0.1 ml/min in halothane anaesthetized rats, and Met-enkephalin-like material (MELM) was measured in 0.5 ml fractions collected from the perifusates. Immersing the muzzle of intact rats in water at 52 degrees C produced a significant enhancement of MELM content in perifusates from both the whole spinal cord and the cervicotrigeminal area but not from the lumbar area. Heating the tail resulted in an increase in MELM release from the whole spinal cord of intact as well as of cervically transected rats. It is concluded that noxious thermal stimuli can induce a segmental release of MELM, i.e., only within spinal zones receiving the nociceptive inputs.

Animals↗
PubMed1989

Neonatal capsaicin treatment abolishes the modulations by opioids of substance P release from rat spinal cord slices.

The possible modulation by opioids of substance P (SP) release at the spinal level was studied using slices of the dorsal half of the rat lumbar enlargement superfused with an artificial cerebrospinal fluid. Capsaicin (0.5 microM) selectively evoked a Ca2+-dependent overflow of SP-like material (SPLI) from primary afferent fibers which was enhanced in the presence of mu-opioid agonists (DAGO, FK 33824, sufentanyl, morphine), reduced by the delta-opioid agonist DTLET, and unaltered by the kappa-opioid agonist U 50488 H. Selective antagonists (naloxone, ICI 154129) prevented the effects of mu- and delta-opioid agonists. Neonatal capsaicin (50 mg/kg) abolished the stimulatory effect of in vitro capsaicin (0.5 microM) but not that of 30 mM K+ on SPLI outflow. This K+-induced SPLI release was unaffected by opioids. Presynaptic inhibitory control of SPLI release from capsaicin-sensitive primary afferent fibers might account for the analgesic effect of delta- but not mu- and kappa-opioid agonists at the spinal level.

Animals↗
PubMed1989

Opioid control of the in vitro release of calcitonin gene-related peptide from primary afferent fibres projecting in the rat cervical cord.

In vitro superfusion of slices from the dorsal half of the rat cervical enlargement allowed the measurement of spontaneous, K+ (30 mM)- and capsaicin (0.5 microM)-evoked release of calcitonin gene-related peptide-like immunoreactive material (CGRPLI). The greater part of this immunoreactive material originated in primary afferent fibres since dorsal rhizotomy from C4 to Th2 (8 days before sacrifice) resulted in a 85-90% decrease in CGRPLI release. CGRPLI outflow which persisted after dorsal rhizotomy could still be enhanced by K+-induced depolarization but was no longer sensitive to the stimulatory effect of 0.5 microM capsaicin. Both delta (DTLET, D-Pen2-D-Pen5-enkephalin) and mu (DAGO, PL 017) opioid receptor agonists reduced the K+ evoked release of CGRPLI from the dorsal half of the cervical enlargement. Morphine was also inhibitory but the selective K opioid agonist U 69593 was inactive. As expected from the involvement of delta and mu receptors, the selective opioid antagonist ICI 174864 and naloxone prevented the inhibitory effects of DTLET and DAGO, respectively. These data suggest that opioid-induced presynaptic inhibiton of CGRP-containing primary afferent fibres may be involved in the analgesic effect of intrathecally injected delta and mu opioid agonists in rats.

Afferent Pathways↗
PubMed1988

Direct stimulatory effect of calcitonin on [3H]5-hydroxytryptamine release from the rat spinal cord.

The in vitro effects of porcine, salmon and human calcitonin on the K+-evoked overflow of [Met5]enkephalin, substance P and [3H]5-HT (previously taken up) were investigated in superfusion experiments with spinal cord slices. Porcine and salmon calcitonin did not affect the release of [Met5]enkephalin and substance P but enhanced that of [3H]5-HT. In contrast, human calcitonin was inactive. The stimulatory effect of porcine and salmon calcitonin on K+-evoked [3H]5-HT overflow was found with slices from the dorsal or the ventral half of the lumbar enlargement but not with hippocampal or hypothalamic slices. The calcitonin effect on [3H]5-HT outflow persisted in the absence of extracellular Ca2+ but was totally suppressed by 5-HT uptake inhibitors such as citalopram and chlorimipramine and by the 5-HT-releasing agent, p-chloroamphetamine. Direct investigation of the possible action of porcine calcitonin on [3H]5-HT uptake and release demonstrated that the enhanced [3H]5-HT overflow resulted from a p-chloramphetamine-like 5-HT-releasing effect of the hormone at the spinal level. This action might be involved in the potent analgesic effect of intrathecal calcitonin.

Animals↗
PubMed1988

Spontaneous and evoked release of met-enkephalin-like material from the spinal cord of arthritic rats in vivo.

Perfusion of the intrathecal space with artificial CSF was achieved in control and arthritic rats under halothane anaesthesia in order to collect the met-enkephalin-like material (MELM) released from the whole spinal cord. On the fourth week following the intradermal injection of Freund's adjuvant to induce arthritis, a marked reduction (-56%) in the spontaneous outflow of MELM was noted in arthritic rats. This effect did not involve changes in the degradation process of MELM, since it persisted when kelatorphan was added to the perfusing fluid in order to inhibit completely the peptidases acting on met-enkephalin. Raising the K+ concentration in the perfusing fluid from 2.4 to 40 mM, as well as moving the hind paws, produced a significant enhancement of MELM release which was (at least) as pronounced in arthritic as in control rats. These results suggest that the basal activity of spinal enkephalinergic neurones, but not that triggered by various stimuli, is reduced in arthritic rats.

Animals↗
PubMed1988

Biochemical mapping of cholecystokinin-, substance P-, [Met]enkephalin-, [Leu]enkephalin- and dynorphin A (1-8)-like immunoreactivities in the human cerebral cortex.

The distribution of immunoreactive cholecystokinin, substance P, [Met]enkephalin, [Leu]-enkephalin and dynorphin was determined in the cerebral cortex of the human brain post mortem. Peptide radioimmunoassays in three selected zones of the cortical gray mantle (frontal, temporal, occipital) revealed significant regional differences, prompting to the development of a new dissection procedure for the complete mapping of peptide-like materials throughout the entire cerebral cortex. For this purpose, frozen cerebral hemispheres were cut rostrocaudally in 21 verticofrontal serial sections, from which the cortical gray matter was divided into 4-5 distinct zones. The peptides could be measured in each of the 93 dissected pieces of tissue, but their distribution was uneven. The most abundant was cholecystokinin, particularly in the anterior part of the frontal lobe and in the temporal cortex, where its levels reached 0.5 ng/mg of tissue. The regional distribution of cholecystokinin resembled that of substance P with a decreasing gradient from the frontal to the occipital pole, but absolute levels of substance P were hardly one tenth of cholecystokinin levels. The mean concentrations of the three opioid peptides were even less than those of substance P, and their regional distributions were markedly different. [Met]Enkephalin was concentrated in the occipital cortex, and [Leu]enkephalin in the temporal cortex. Dynorphin was the least abundant, even in the temporal cortex where the highest levels were found. The widespread and heterogeneous distribution of these peptides strongly suggests that each of them exerts specific functions in the human cerebral cortex.

Aged↗
PubMed1988

Angiotensin II-like material extracted from the rat brain is distinct from authentic angiotensin II.

Specific radioimmunoassay and radioreceptor assay for angiotensin II (A II) were used for the possible identification of this peptide in the rat brain. An A II-like material (A II-LM) was detected with both assays applied to acidic extracts of various brain structures. The regional distribution of A II-LM was uneven, but absolute levels (in A II equivalents) could not be accurately determined, as they were highly dependent on the assay used. Partial purification of A II-LM by Sep-Pak C 18 chromatography and affinity chromatography using anti-A II antibodies bound to Ultrogel gave a compound coeluting with authentic A II in reverse-phase HPLC. However, gel filtration through Sephadex G-25 and TSK Spherogel 3000 SW as well as anion exchange HPLC demonstrated that A II-LM did not correspond to authentic A II. Partial characterization of A II-LM indicated that this compound was probably a peptide with an apparent molecular weight of 5,000-7,000 (instead of 1,046 for A II) and more polar but less positively charged than A II. Whether A II-LM is, in fact, the endogenous ligand of A II binding sites in brain remains an interesting hypothesis for further investigations.

Angiotensin II↗
PubMed1987

Involvement of the dorsolateral funiculi in the spinal release of Met-enkephalin-like material triggered by heterosegmental noxious mechanical stimuli.

The lumbar spinal cord was superfused with artificial CSF at a rate of 0.1 ml/min in halothane anaesthetized rats. Under resting conditions, Met-enkephalin-like material (MELM) found in superfusates corresponded to a spinal release of 4.2 +/- 1.4 pg Met-enkephalin equivalents per 5 min. During a 30-min period in which pinches were applied to the muzzle, the MELM content in the superfusates increased markedly (by 120.5 +/- 32.9%). This effect was totally suppressed following bilateral lesions of the dorsolateral funiculi (DLF), under both chronic and acute conditions. It is concluded that strong mechanical stimuli applied in the trigeminal region can induce the release of MELM within the lumbar spinal cord via mechanisms involving the DLF. This heterosegmental release of Met-enkephalin may participate in the management of pain by methods involving high intensity stimulation.

Animals↗
PubMed1987

Brain neuropeptides in progressive supranuclear palsy.

No significant alterations in the levels of Met-enkephalin-, Leu-enkephalin-, cholecystokinin- and substance P-like immunoreactive materials were found in 10 areas of postmortem brains from patients with progressive supranuclear palsy (PSP) when compared to controls. These results are at difference with the marked decrease in the levels of enkephalin-, cholecystokinin- and substance P-like immunoreactive materials previously reported in the basal ganglia of parkinsonian patients. Since PSP and Parkinson's disease are both characterized by a severe dopamine nigrostriatal deficit, these results suggest that the decreased brain peptide concentrations found in Parkinson's disease do not simply result from a dopaminergic neuronal loss.

Aged↗
PubMed1987

Noxious mechanical stimuli increase the release of Met-enkephalin-like material heterosegmentally in the rat spinal cord.

Although the physiological functions of the endogenous opioid systems are not yet clearly established, it is widely accepted that they exert an inhibitory control on pain transmission. However, the well-documented hypoalgesic effects of low doses of the opiate antagonist naloxone both in animals and humans do not fit in with this concept. The present investigations, at two different spinal/medullary levels (viz. cervicotrigeminal and lumbar) demonstrate that, in the rat, a noxious mechanical stimulus does not alter the release of Met-enkephalin-like material (MELM) from neural segments related to the stimulated area of the body, but does increase its release from other segments. Electrophysiological studies have already demonstrated the existence of such heterosegmental mechanisms, notably 'diffuse noxious inhibitory controls' (DNIC), which are naloxone-reversible and could play an important role in pain perception. The involvement of spinal enkephalins in DNIC would seem to mean that the heterosegmental spinal release of MELM triggered by noxious stimuli participates in pain processes.

Animals↗
PubMed1987

Opioid receptors and neuropeptides in the CNS in rats treated chronically with amoxapine or amitriptyline.

The central mechanism responsible for the potentiation by antidepressant drugs of analgesia induced by morphine, was explored by measuring the levels of various neuropeptides (met-enkephalin, leu-enkephalin, dynorphin, substance P and cholecystokinin-like materials) and the density of delta and mu opioid binding sites in the spinal cord of rats treated for 14 days with amoxapine (10 mg/kg i.p., daily) or amitriptyline (10 mg/kg i.p., daily). Similar measurements were made in the hypothalamus and cerebral cortex for comparison. Chronic treatment with amoxapine or amitriptyline did not affect the levels of dynorphin, substance P and cholecystokinin, but markedly enhanced the levels of leu-enkephalin in the three structures examined. The levels of met-enkephalin were also increased after treatment with amitriptyline but only in the spinal cord and hypothalamus. No changes in opioid receptors were found in the cerebral cortex, but the densities of delta and mu opioid binding sites were increased in the spinal cord, and decreased in the hypothalamus of rats treated with amoxapine or amitriptyline. These changes induced by antidepressants in opioidergic markers at the spinal level might account for the potentiation of the action of morphine in amoxapine- or amitriptyline-treated rats. In addition, the observed alterations in the same markers in the hypothalamus could be associated with changes induced by antidepressants in neuroendocrine regulation.

Amitriptyline↗
PubMed1987

Chronic chlorimipramine does not reverse the reduction of cerebrospinal fluid Met-enkephalin-like immunoreactivity in chronic-pain patients.

Chronic-pain patients were treated for 10 days with chlorimipramine (100 mg i.v. daily), and their plasma levels of the drug and cerebrospinal fluid (CSF) levels of Met-enkephalin-like material (MELM) were measured for a comparison with those found in untreated chronic-pain patients and in control subjects. Pain relief in chlorimipramine-treated patients was apparently not associated with pronounced changes in the activity of enkephalinergic systems since the mean CSF levels of MELM were reduced to the same extent in treated (-49%) and untreated (-45%) pain patients as compared with controls. However, subtle chlorimipramine-induced alterations likely occurred as revealed by the simultaneous measurement of the CSF levels of 5-hydroxyindoleacetic acid (5-HIAA) in the same patients. Indeed, a positive correlation (r = 0.667) was found between CSF 5-HIAA and MELM levels in control subjects, whereas a negative correlation (r = 0.691) between these two parameters was detected in chlorimipramine-treated patients. These data suggest that chlorimipramine alters probable functional serotonin-enkephalin interactions in pain patients.

Adult↗