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J L Junien

Publications and source records attributed to J L Junien.

At least 55 records · Page 3Linked to original sources
PubMed1994

A C-fiber reflex modulated by heterotopic noxious somatic stimuli in the rat.

1. Electromyographic recordings were made from the biceps femoris muscle through a pair of noninsulated platinum/iridium needle electrodes in male Sprague-Dawley rats artificially ventilated and anesthetized with 0.8% halothane in a N2O-O2 mixture (2/3:1/3). The animals' ventilation, heart rates, and body temperatures were continuously monitored. Electrical stimuli (2-ms duration, 0.16 Hz) were delivered to the sural nerve territory through a pair of noninsulated platinum/iridium needle electrode inserted subcutaneously in the medial aspect of the 4th and the lateral part of the 5th toe. Such stimulation elicited a two-component reflex response in the ipsilateral biceps femoris muscle: The first had a short latency (17.5 +/- 2.3 ms), short duration (20.7 +/- 2.6 ms), and low threshold (1.5 +/- 0.6 mA), whereas the second had a longer latency (162.4 +/- 5.1 ms), longer duration (202.3 +/- 6.2 ms), and higher threshold (5.7 +/- 0.5 mA). 2. Lidocaine (0.02-0.1%; 0.1 ml), but not saline, injected subcutaneously over the proximal part of the sural nerve, produced a selective depression of the late component of the reflex response, whereas the first component remained unchanged. The conduction velocity of the afferent fibers was estimated from the stimulation needles in the sural nerve territory to the nerve's projection in the lumbar spinal cord: it was concluded that the second, late component of the reflex response was due to afferent signals transmitted via unmyelinated C-fibers, whereas the first component was related to activation of fine myelinated fibers (A delta group). 3. Electrical stimulation of the sural nerve was still able to elicit the two-component reflex responses in the ipsilateral biceps femoris muscle of chronic spinal rats, indicating that these responses were genuine reflex responses, transmitted completely through a spinal circuit. 4. The C-fiber reflex was recorded when the duration and frequency of the stimuli applied to the sural nerve varied within the 0.5- to 4-ms and 0.02- to 1-Hz ranges, respectively. It was concluded that a single 2-ms duration shock at an intensity of 1.2 times the C-fiber reflex threshold, delivered every 6 s (0.16 Hz), constituted an acceptable and optimal protocol for experiments in which the C-fiber reflex was studied as a function of time. These parameters were used throughout the subsequent experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1994

Tonic regulation of mouse ileal ion transport by nitric oxide.

The possible role of nitric oxide (NO) in the regulation of intestinal ion transport was studied in isolated sheets of mouse ileum mounted in Ussing flux chambers. The competitive NO-synthase inhibitors NG-methyl-L-arginine (L-NMA), and NG-nitro-L-arginine (L-NNA) and the effects of NO released from acidified sodium nitrite solution were evaluated in tissues pretreated with guanethidine and atropine. Serosal L-NMA or L-NNA (10-300 microM), but not NG-methyl-D-arginine (D-NMA), produced a sustained concentration-related increase in short-circuit current (Isc) and potential difference (PD) with maximal Isc increases of 50.8 +/- 8.2 and 45.5 +/- 5.8 microAmps/cm2, respectively; mucosal application of L-NMA or L-NNA produced transient increases in Isc. The A50 (and 95% CL) values for serosal L-NMA and L-NNA were 25.6 (15.7-41.9) and 8.7 (5.1-14.9) microM, respectively. L-Arginine (0.1-10 mM), but not D-arginine, produced both a concentration-related reversal of L-NMA or L-NNA-induced increases in Isc. Additionally, pretreatment with L-arginine blocked the L-NMA or L-NNA effects, suggesting a competitive interaction. L-NMA-mediated increases in Isc were unaffected by bicarbonate-free buffer, whereas replacement of chloride ions with gluconate ions almost completely attenuated the response to L-NMA. Further, the effects of L-NMA or L-NNA were blocked by tetrodotoxin or chlorisondamine, suggesting neural actions involving ganglionic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1994

Fedotozine reversal of peritoneal-irritation-induced ileus in rats: possible peripheral action on sensory afferents.

Two kappa agonists, fedotozine and trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolydinyl)-cyclohexyl ]- benzeneacetamide methanesulfonate [(+/-)U-50,488H] were used to reverse the gastrointestinal transit inhibition induced by either peritoneal irritation (PI) or intracisternal (i.c.) administration of corticotropin releasing factor (CRF). PI was induced by acetic acid given i.p. Gastric emptying and intestinal transit were estimated with a 51Cr-labeled test meal. PI inhibited both gastric emptying (-50.9%) and intestinal transit (-48.8%). These inhibitions were prevented in a dose-dependent manner by the CRF antagonist, alpha-helical-CRF9-41 at doses (1-10 nmol/rat i.c.) that had no effect in control animals. CRF (300 pmol/rat i.c.) reproduced the gastrointestinal transit inhibitions seen under PI. The CRF effects were blocked by alpha-helical-CRF9-41 (10 nmol/rat) given i.c. but not i.v. Fedotozine (1-10 mg/kg s.c. but not 300 micrograms/rat i.c.v. or intrathecally) and (+/-)U-50,488H (0.3-3 mg/kg s.c. but not 100 micrograms/kg i.c.v.) reversed PI- but not CRF-induced ileus. Neither PI-induced ileus nor the fedotozine response was affected by perivagal capsaicin treatment. It was concluded that the PI-induced ileus depends on central CRF receptors. This result is consistent with the activation of an extrinsic inhibitory reflex. The reversal by kappa agonists of PI- but not CRF-induced ileus suggests that kappa agonists do not act after but before the CRF receptors. A possible peripheral action on nonvagal sensory afferents is suggested.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

In vivo interaction of neuropeptide Y and peptide YY with sigma receptor sites in the mouse brain.

Neuropeptide Y (NPY-(1-36)), peptide YY (PYY) and various other peptides were investigated for their interaction with the binding of [3H](+)-SKF10,047 to sigma binding sites in mouse hippocampus in vivo. NPY-(1-36), PYY-(1-36), [Leu31,Pro34]NPY, NPY-(2-36), and NPY-(3-36) inhibited the labelling of a population of haloperidol-sensitive binding sites corresponding to 35% of the specific binding. These in vivo binding results confirm the previous interaction already reported between NPY peptides and sigma binding sites.

Animals↗
PubMed1993

Comparative involvement of 5-HT1, 5-HT2 and 5-HT3 receptors in stress-induced colonic motor alterations in rats.

The role of 5-HT1, 5-HT2 and 5-HT3 receptors in the genesis of colonic motor alterations induced by emotional stress was evaluated in rats equipped with implanted nickel/chrome electrodes on the proximal colon and a catheter into the lateral ventricle of the brain. In control rats the frequency of colonic spike bursts increased from 7.6 +/- 1.3 to 16.8 +/- 1.3 per 10 min when the rats were placed in a test cage in which they had previously received electric footshocks. I.p. injection of methysergide (0.1 mg/kg) reduced by 54% the emotional stress-induced increase of colonic spike burst frequency, while a higher dosage (1 mg/kg) of methysergide had no effect. The i.p. injection of ketanserin (a 5-HT2 receptor antagonist, 0.1 and 1 mg/kg) or granisetron (a 5-HT3 receptor antagonist, 0.1 and 1 mg/kg) had no effect on emotional stress-induced colonic hyperkinesia. The i.p. injection of the 5-HT1A receptor agonists, buspirone (1 mg/kg) or 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino(tetralin) (0.05 and 0.1 mg/kg) or benzodiazepine (clonazepam, 1 mg/kg) significantly reduced or suppressed the emotional stress-induced increase of colonic spike bursts. Injected i.c.v., buspirone, but not 8-OH-DPAT, also reduced the emotional stress-induced hyperkinesia. Pretreatment with devazepide receptor (1 microgram/kg) antagonized the inhibitory effects of buspirone and 8-OH-DPAT injected i.p. on emotional stress-induced colonic hyperkinesia but did not alter the effects of clonazepam (1 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Neuropeptide Y and sigma receptor agonists act through a common pathway to stimulate duodenal alkaline secretion in rats.

Neuropeptide Y (NPY) has been shown to mimic the effects of some sigma receptor agonists in the brain and to possess the same proabsorptive effect as these agonists in the isolated mouse jejunum. The aim of present study was to investigate the effect of NPY on duodenal alkaline secretion in the rat and to define its mode of action. NPY (0.01 to 3 micrograms/kg i.v.) induced a dose-related increase in duodenal bicarbonate secretion, the maximal effect being obtained at 1 micrograms/kg. This response was significantly inhibited by the i.v. administration of haloperidol, BMY 14802, devazepide, hexamethonium, tetrodotoxin and by bilateral truncal vagotomy, but not by SCH 23390, sulpiride, prazosin or atropine, whereas i.c.v. devazepide had no effect. This pharmacological profile is identical to that reported for sigma receptor agonists. The results suggest that NPY and sigma ligands act through a common pathway to stimulate duodenal alkaline secretion in the rat.

Animals↗
PubMed1993

Repeated administration of Sigma ligands alters the population activity of rat midbrain dopaminergic neurons.

Acute and repeated administration of antipsychotic drugs produce distinctive profiles of electrophysiological effects on the population activity of midbrain dopaminergic (DA) neurons which correlate with their clinical effects. Sigma receptors have been hypothesized to be involved in psychosis and in the efficacy of antipsychotic drugs, but little is known about the effects of repeated treatment with sigma ligands on the activity of midbrain DA neuronal populations. In the present study, the cells-per-track cell-sampling method was used to evaluate the effects of 3 sigma ligands on the numbers of spontaneously active A9 and A10 DA neurons in chloral hydrate-anesthetized rats. One-hour pretreatment with either (+)-pentazocine (10 mg/kg, i.p.), DTG (2 mg/kg, i.p.), or JO 1784 (1 or 10 mg/kg, s.c.) did not alter the number of spontaneously active DA neurons encountered per electrode track. Repeated treatment (21 daily injections) with (+)-pentazocine (1 or 10 mg/kg) or DTG (0.2 or 2 mg/kg) increased the number of A10 DA cells per track; JO 1784 (10 mg/kg but not 1 mg/kg) moderately decreased the number of active A9 DA cells and increased the firing rate of A10 DA neurons. The effect of JO 1784 on A9 DA neurons was not due to depolarization inactivation. The effects of all 3 sigma ligands differ from those of antipsychotic drugs, all of which inactivate A10 DA neurons after repeated treatment. Clinical studies are necessary to determine if selective sigma ligands will provide a novel alternative to DA antagonists in the treatment of psychosis.

Animals↗
PubMed1993

Effects of a new sigma ligand, JO 1784, on cysteamine ulcers and duodenal alkaline secretion in rats.

BACKGROUND: The ulceroprotective effects of JO 1784 [(+)-N-cyclopropyl-methyl-N-methyl-1,4-diphenyl-1-ethyl-but-3-en-1-yl amine, hydrochloride], a new specific and highly selective sigma ligand, were examined in rats. METHODS: Different models of gastric ulcers (4-hour restraint stress, aspirin, ethanol, and taurocholate) and cysteamine-induced duodenal ulcers were used. The gastric acid secretion (4-hour Shay rat preparation) and the duodenal bicarbonate secretion were also studied. RESULTS: JO 1784 elicited a potent protection against duodenal ulcers but had a weaker protective effect on any of the gastric ulceration models tested. It displayed no gastric antisecretory activity but induced a dose-dependent stimulation of duodenal bicarbonate secretion. Haloperidol, hexamethonium, tetrodotoxin, bivagotomy (but not atropine), and the intravenous but not intracerebroventricular administration of devazepide, a cholecystokinin A antagonist, inhibited the stimulatory effect of JO 1784. CONCLUSION: These results show that JO 1784, a selective sigma ligand, is a potent protector of the duodenal mucosa. This activity may be related to its stimulating effect on bicarbonate secretion, which is driven through a complex nervous mechanism involving muscarinic synapses, vagal afferent fibers, and peripheral cholecystokinin receptors. This drug might open a new specific way in the treatment of duodenal ulcers.

Animals↗
PubMed1993

Fedotozine reverses ileus induced by surgery or peritonitis: action at peripheral kappa-opioid receptors.

BACKGROUND: Fedotozine is a peripheral opioid agonist. Its effects were assessed in experimental ileus in rats. METHODS: Ileus was induced by abdominal surgery (laparotomy and cecum palpation) or peritonitis (acetic acid, intraperitoneally). Digestive motility was recorded by electromyography and gastrointestinal transit estimated using a 51Cr-labeled test meal. RESULTS: Surgery or peritonitis inhibited motility and migrating myoelectrical complexes for 2-3 hours. In both models, fedotozine (3 mg/kg, intravenously; 10 mg/kg, subcutaneously) restored a normal motility pattern. This action was reproduced by the kappa-agonist, U-50, and 488H and was blocked by subcutaneous naloxone, naloxone-methiodide, or nor-binaltorphimine, a selective kappa-antagonist. Peritonitis induced a 57% inhibition of gastric emptying and intestinal transit that was reversed by fedotozine (1-10 mg/kg, subcutaneously) or kappa-agonists (U-50, 488H, bremazocine) but not delta-agonists (DPDPE, [D-Ala2]-deltorphin-II), whereas mu-agonists (morphine, fentanyl) potentiated ileus. Fedotozine restoration of transit was blocked by subcutaneous naloxone, naloxone-methiodide, or norbinaltorphimine but not by intracerebroventricular naloxone. Fedotozine was inactive up to 300 micrograms/rat when given intracerebroventrically or intrathecally. CONCLUSION: Fedotozine reverses experimental ileus via an action at peripheral kappa-opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Effects of neuropeptide Y, peptide YY and sigma ligands on ion transport in mouse jejunum.

The effects of putative sigma ligands and two neuropeptides on intestinal ion transport were evaluated in isolated sheets of whole mouse jejunum mounted in Ussing flux chambers. Serosal administration of neuropeptide Y (NPY), peptide YY (PYY), (+)-N-cyclopropylmethyl-N-methyl-1,4- diphenyl-1-ethyl-but-3-en-1-ylamine hydrochloride (JO 1784), di(ortho-tolyl)guanidine (DTG) and (+)- or (-)-N-allyl-normetazocine (NANM) produced concentration-related decreases in short-circuit current (Isc) without changes in tissue conductance. Although NPY and PYY were active in nanomolar concentrations, JO 1784, DTG and (+)- and (-)-NANM were active in micromolar concentrations; the rank order of potency in inhibiting Isc was PYY > NPY >> JO 1784 = (-)-N- cyclopropylmethyl-N-methyl-1,4-diphenyl-1-ethyl-but-3-en-1-ylamine hydrochloride > DTG > (+)-NANM = (-)-NANM. Serosal application of tetrodotoxin effectively blocked the decrease in Isc associated with all of the ligands tested. The activity of the serosally applied ligands was blocked by prior application of chlorisondamine, a ganglionic blocker. The effects of JO 1784 and NPY were evaluated using antagonists of several receptor types. Although application of serosal haloperidol had no effect alone up to concentrations of 1 microM, this compound produced a rightward displacement in both the NPY and JO 1784 concentration-effect curves. In contrast, sulpiride, SCH-23390, naloxone, yohimbine and prazosin failed to antagonize the effects of NPY or JO 1784.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Central action of sigma receptor ligand, JO 1784, to suppress CRF-induced inhibition of gastric function in conscious rats.

The central interaction between the sigma receptor ligand, JO 1784, and corticotropin-releasing factor (CRF)-induced inhibition of gastric acid secretion and emptying was investigated in conscious rats. Intracisternal (i.c.) injection of CRF (5 micrograms) inhibited by 95% gastric acid secretion. JO 1784 (0.05-0.5 micrograms) given i.c. immediately before i.c. injection of CRF partially reversed CRF antisecretory action whereas JO 1784 (5 micrograms) given i.v. had no effect. CRF (0.6 micrograms i.c.)-induced 83% inhibition of gastric emptying was reversed by 45% by JO 1784 (5 micrograms i.c.). JO 1784 (5-50 micrograms i.c.) did not influence basal gastric function. These data demonstrate a centrally mediated antagonistic action of the sigma receptor ligand, JO 1784, on i.c. CRF-induced inhibition of gastric function.

Animals↗
PubMed1992

Regional differences in the effect of N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP) on extracellular dopamine levels: an in vivo microdialysis study.

N-[1-(2-Benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP) is a phencyclidine derivative highly selective for the dopamine (DA) uptake complex. Its effect on extracellular DA levels was studied by in vivo microdialysis on freely moving rats. In the striatum, BTCP induced a dose-dependent increase in DA levels, without affecting DA metabolites. In the nucleus accumbens, a lower increase in DA was observed, but with concomitant decreases in 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). These experiments show that the effects of BTCP on extracellular DA levels are significantly different on extrapyramidal and mesolimbic dopaminergic terminals.

Animals↗
PubMed1992

Acute effects of sigma ligands on the electrophysiological activity of rat nigrostriatal and mesoaccumbal dopaminergic neurons.

The effects of acute i.v. administration of several sigma ligands on the single-unit activity of nigrostriatal and mesoaccumbal dopaminergic (DA) neurons were evaluated in chloral hydrate-anesthetized rats. DTG (1,3-di(o-tolyl)guanidine) did not alter DA neuronal activity at nontoxic doses and JO 1784 [(+)-N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1-ethylbut-3-en-1-+ ++ylamine] was inactive. (+)-Pentazocine was more effective in increasing mesoaccumbal vs. nigrostriatal DA cell firing rates. BMY 14802(alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-but anol) dose-dependently increased DA cell firing rate in both populations. The inhibition of nigrostriatal DA cell firing rate by (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)-3-PPP] was reversed by (-)-eticlopride and (+)-but not (-)-butaclamol, which supports previous evidence that (+)-3-PPP-induced inhibition is due to the DA agonist properties of the drug. From what is known of the pharmacological properties of these compounds, it is concluded that acute sigma receptor occupation does not markedly alter the firing rate of DA neurons. The dose-response curve for inhibition of nigrostriatal DA neuronal activity by the D2 DA agonist, quinpirole, was shifted to the right tenfold by BMY 14802 pretreatment (8 mg/kg, i.v.) and twofold by (+)-pentazocine (8 mg/kg, i.v.), but was not changed by DTG (2 mg/kg, i.v.). It is concluded that the marked effects of certain sigma ligands on DA cell electrophysiology are likely due to their non-sigma properties.

Animals↗
PubMed1992

Dog gastric lipase: stimulation of its secretion in vivo and cytolocalization in mucous pit cells.

Dog gastric lipase (DGL) secretion is stimulated in vivo by urecholine, pentagastrin, histamine, 16,16-dimethyl prostaglandin E2, and secretin. Under fasting conditions, DGL is irreversibly inactivated by gastric acid below pH 1.5; consequently, DGL output can be underestimated. This problem has been resolved by buffering the acid or by using an antisecretory drug such as omeprazole during stimulation. There is a clear parallelism between the secretion of DGL and of gastric mucus. This observation led to the present investigation of the cellular localization of DGL using immunofluorescence techniques. Results showed that DGL is cytolocalized in mucous pit cells of gastric glands. Pepsinogen is found in chief cells. To the authors' knowledge, this is the first description of an enzyme (gastric lipase) secreted by mucous-type gastric cells. In contrast to other species, gastric lipase of the dog is located in cardiac, fundic, and antral mucosae.

Animals↗
PubMed1992

Role of opioids in peripheral analgesia.

Several pharmacological, neurophysiological and immunohistological studies indicate that exogenous or endogenous opioids can have antinociceptive effects by acting at peripheral sites. Although modulation of mu, delta and kappa receptors can mediate these effects, the nature of the noxious stimulus and the underlying pathological condition may affect the types of opioid receptors involved. Thus, it would be appropriate to develop peripherally-acting opioid analgesics that do not have the untoward central side effects often associated with conventional analgesic drugs. This paper reviews the evidence supportive of a peripheral mechanism of action for opioids.

Analgesia↗
PubMed1992

Travel stress alters the intestinal migrating myoelectric complex in rats: antagonist effect of trimebutine.

A novel stress model was developed that may closely resemble a real-life situation. Intestinal motility was monitored in rats before and after a 12 hour train voyage (travel stress). Travel stress reduced the duration of phase III of the intestinal MMC by 30% (3.2 +/- 0.3 vs 4.7 +/- 0.6 min; p less than 0.001) while the durations of phase I and II were unaffected. This effect persisted for two days. Phase III duration returned to basal values after 3 days indicating a reversible alteration on intestinal migrating myoelectric complex (MMC). The infusion of trimebutine at a flow rate of 166 micrograms/kg/h during the stress exposure abolished the changes observed in the duration of phase III of the MMC; the infusion of diazepam (16.6 micrograms/kg/h) had no effect. These results indicate that the travel stress model may be similar to common life events that induce alterations of intestinal motility. Furthermore, trimebutine prevented the reduction of phase III duration induced by travel stress suggesting its possible action on mechanisms involved in the mediation of the stress-induced intestinal motility changes.

Animals↗
PubMed1992

Effects of 5-HT3 antagonists on fixed-interval behavior in rats.

The effects of 5-hydroxytryptamine3 (5-HT3) antagonists were studied in rats responding under a fixed-interval (FI) schedule of food presentation. BRL 43694, GR 38032F, ICS-205,930 and zacopride had no effect on FI responding up to 10.0 mg/kg IP. Response rate decreases were observed only at high doses (30.0 or 56.0 mg/kg); rate increases were not observed. In comparison, caffeine (1.0-10.0 mg/kg) and cocaine (3.0-18.0 mg/kg) increased and lorazepam (0.3 mg/kg) decreased FI responding. The effects of caffeine, cocaine, and lorazepam were unchanged when coadministered with the 5-HT3 antagonists. The results show that 5-HT3 antagonists, when given alone or with other CNS-active drugs, have little effect on FI responding of rats.

Animals↗