摘要:

The present study examined whether the effect of stimulation of the nucleus raphe magnus (NRM) is mediated by spinal cord dorsal horn serotonin1A (5-HT1A) receptors in the rat. This hypothesis predicts that nociceptive dorsal horn units inhibited by NRM stimulation or iontophoretic 5-HT application would also be inhibited by iontophoresis of the selective 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and buspirone. A total of 78 dorsal horn wide-dynamic-range neurons were recorded. Overall, 62% of the cells tested (48/78) were responsive to electrical stimulation of the NRM with the predominant response being inhibitory (38/48; 79%). Fifty-eight cells were tested for their response to both NRM stimulation and 8-OH-DPAT iontophoresis: 20/58 cells were inhibited by NRM stimulation and 50% of the cells inhibited by NRM stimulation were also inhibited by 8-OH-DPAT. Fifty-two cells were tested for their response to both NRM stimulation and buspirone iontophoresis: 14/52 cells were inhibited by NRM stimulation with 9/14 similarly inhibited by buspirone. To examine whether exogenously applied serotonin produced an effect through 5-HT1A receptors, the effect of both 5-HT and 8-OH-DPAT iontophoresis was tested on 57 dorsal horn neurons. The majority of cells (25/57) were inhibited by 5-HT application; 15/25 were similarly inhibited by 8-OH-DPAT. The response of 48 dorsal horn cells to 5-HT and buspirone iontophoresis was compared. Forty-four percent (21/48) of the cells were inhibited by 5-HT; 16/21 were also inhibited by buspirone. The present data support the hypothesis that 5-HT1A receptors mediate the inhibitory effect of the NRM descending 5-HT pathway on spinal pain transmission. These results are surprising in that 5-HT1A receptors represent approximately 25–35% of dorsal horn 5-HT receptors and that the 5-HT system is only one of several descending bulbospinal pathways arising from the NR

ISSN:0031-7012    

DOI:10.1159/000139156

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The mode of action of muramyl dipeptide (MDP), a compound with immunopharmacological properties, was studied in isolated nerve smooth muscle preparations with different receptor systems. The amplitudes of contractions evoked directly by stimulants as well as neurogenic twitches or relaxations were registered. In the rat stomach strip EC50 of acetylcholine, serotonin (5-HT) and KC1 was estimated. MDP (50 nmol/l) but not levamisole potentiated selectively the contractions evoked by 5-HT and significantly (p < 0.01) lowered the respective EC50. In the rat vas deferens MDP selectively potentiated the twitches enhanced by 5-HT but not those enhanced by noradrenaline. Such potentiation was blocked by 5-HT3 antagonists tropisetron and MDL 72 222 (lαH,3α,5α-H-tropan-3-yl 3,5-dichlorobenzoate) but not by the 5-HT2 antagonist ketanserin. The antagonist methiothepin nonselectively abolished the potentiation by MDP as well as the enhancement of twitches by 5-HT and noradrenaline, whereas l-propranolol and isamoltan influenced neither the enhancement of twitches by 5-HT nor the potentiation by MDP. In the isolated longitudinal muscle of guinea pig proximal colon, 5-HT caused a biphasic response in the presence of atropine; the initial neurogenic relaxation was potentiated in the presence of MDP and was suppressed in the presence of tropisetron. Thus, the potentiating effect of MDP in the isolated organs studied was selective with respect to the serotoninergic system and might be mediated by 5-HT3 recepto

ISSN:0031-7012    

DOI:10.1159/000139157

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Effects of clonidine and lidocaine on the hyperpolarizing after-potential (HAP) and frequency-dependent block in C fibers were examined on desheathed rabbit vagus nerves, using the sucrose gap technique. A single action potential (AP) was followed by a fast and a slow HAP. Clonidine, at concentrations from 0.05 to 50 µmol/l, decreased the fast HAP, while the AP amplitude was unchanged. At a 500 µmol/l concentration of clonidine, the fast HAP amplitude was similar to control, the slow HAP was increased, and the AP amplitude decreased. Lidocaine at 500 µmol/l delayed and broadened the HAP, making a distinction between fast and slow HAP impossible, and decreased and delayed the AP amplitude. In the presence of lidocaine (500 µmol/l), clonidine at concentrations from 0.05 to 500 µmol/l decreased the HAP amplitude, without modifying the lidocaine-induced shape of the HAP. The modifications of the HAP, however, do not contribute to the local anesthetic effects of clonidine, as the addition of clonidine (0.5 and 500 µmol/l) to Locke or lidocaine (500 µmol/l) solution does not enhance the frequency-dependent block (3 and 10 Hz) observed with either Locke or lidocaine solution

ISSN:0031-7012    

DOI:10.1159/000139158

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Midazolam, a benzodiazepine receptor agonist, when injected intrathecally either enhances or decreases antinociception produced by intrathecal administration of morphine in rats. Furthermore, midazolam inhibits binding of several opioid ligands to spinal opioid receptors in vitro [Rattan et al, Anesth Analg 1991;73:124–131]. This study was designed to investigate the effect of midazolam on binding of µ-, δ- and ĸ-ligands to rat spinal opioid receptors in the presence of sodium ions which differentially modulate binding of opioid agonists and antagonists. Sodium ions (50-1,000 mmol/l) selectively increased the specific binding of [3H]naloxone but decreased binding of opioid agonists such as [3H]DAGO (Tyr-D-Ala-Gly-Methyl-Phe-Gly-ol-enkephalin) to µ-receptors, [3H]DSTLE (Tyr-D-Ser-Gly-Phe-Leu-Thr-enkephalin) to δ-receptors and [3H]EKC (ethylketocyclazocine) to ĸ-receptors in rat spinal cord in vitro. Midazolam (1-100 µmol/l) inhibited the binding of [3H]naloxone, [3H]DAGO, [3H]DSTLE and [3H]EKC. Sodium ions (100 mmol/l) antagonized the inhibition of binding of [3H]naloxone and [3H]DSTLE by midazolam by increasing IC50 values for midazolam. However, sodium ions potentiated the inhibition of binding of [3H]DAGO by midazolam by decreasing IC50 value for midazolam and had a mixed effect on binding of [3H]EKC in the presence of midazolam. Scatchard analysis performed in the presence of sodium ions and/or midazolam confirmed the specific effects of sodium ions as well as midazolam on the Bmax and Kd of µ-, δ-, and K-receptors. These results suggest for the first time that sodium ions play an important role in the modulation of spinal opioid receptors by benzodiazepines. Sodium ions potentiate the inhibition of DAGO binding but antagonize the inhibition of naloxone and DSTLE binding by midazolam in rat s

ISSN:0031-7012    

DOI:10.1159/000139159

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

This study was designed to test in the dog heart the hypothesis that local levels of myocardial cyclic AMP (cAMP) would exhibit significant heterogeneity; that this heterogeneity would correlate with local coronary blood flow, and that this association would be increased with isoproterenol stimulation. Anesthetized open-chest dogs were studied during control (n = 7) or isoproterenol (0.5 µg/kg/min) infusion (n = 7) to test this hypothesis. Coronary blood flow was measured with radioactive microspheres, and cAMP was determined with a competitive binding assay using 3H-cAMP. Significant heterogeneity in cAMP existed during basal [592 pmol/g, within-animal coefficient of variation (100 × mean/SD) = 45.2%] and isoproterenol stimulated [872 (27.3%)] conditions. Method variability could account for only 28% of the total basal variability. No correlation between local blood flow [87 ml/min/ 100 g (12.9%)] and local cAMP was found under control conditions. Both coronary blood flow [206 (20.8%)] and cAMP levels increased significantly with isoproterenol stimulation. There was a significant correlation between normalized stimulated blood flow and cAMP: % flow = 0.39 (% cAMP) + 61.3 (r = 0.48, p < 0.0001). We conclude that significant heterogeneity in myocardial cAMP levels exists, and that this heterogeneity correlates with coronary blood flow heterogeneity during isoproterenol stimulatio

ISSN:0031-7012    

DOI:10.1159/000139160

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

We have investigated the effects of a novel calcium antagonist, fantofarone (SR 33557) on myocardial oxygen consumption (MO2C) and coronary blood flow in anaesthetized dogs during periods of normal and elevated heart rate. 25 µg/kg i.v. fantofarone induced a transient increase in coronary blood flow (+25% after 2 min; p < 0.05) and a more sustained decrease in MO2C (–50% after 5 min; p < 0.05). During the periods of pacing, these alterations on cardiac function were not evident. Administration of 50 µg/kg i.v. resulted in similar modifications of cardiac function; however, these changes were apparent for a longer duration. Coronary blood flow was still significantly elevated by 29% 2 min after drug administration (p < 0.01) and MO2C was reduced by 67% after 5 min (p < 0.01) and by 56% after 30 min (p < 0.05). Most importantly, a significant decrease in MO2Cwas observed during the pacing periods (32% after 10 min; p < 0.01). Thus fantofarone can significantly modify cardiac function and in particular, decrease MO2Cconsumption during periods of elevated heart r

ISSN:0031-7012    

DOI:10.1159/000139161

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

This study was designed to determine the cytoprotective properties of quercetin and the involvement of endogenous prostaglandins in mucosal injury produced by absolute ethanol. Gastric glands were also analyzed histologically. Oral pretreatment with the highest dose of quercetin (200 mg/kg), 120 min before absolute ethanol, was most effective in necrosis prevention. Subcutaneous administration of indomethacin (10 mg/kg) to the animals treated with quercetin (200 mg/kg) partially inhibited gastric protection. All treated groups showed a marked increase in the amount of gastric mucus although this increase was less in animals pretreated with indomethacin. Total proteins and the hexosamine content decreased in the groups receiving indomethacin. The histomorphometric evaluation of the gastric damage confirmed a significant increase in mucus production accompanied by a parallel reduction of gastric lesions with the highest dose of quercetin tested.

ISSN:0031-7012    

DOI:10.1159/000139162

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Interferons are recognized to inhibit collagen production. Since fibrosis has been associated with liver dysfunction, we investigated the effects of α-interferon on the function and lipid composition of hepatocyte and erythrocyte plasma membranes derived from CCU-cirrhotic male Wistar rats. In both cell types, CCI4 decreased Na+/K+ and Ca2+-ATPase activity and increased the cholesterol to phospholipids (CH/PL) ratio (p < 0.05). Administration of interferon (80,000 IU/kg s.c. for 8 weeks) increased survival from 40 to 90%, and preserved normal ATPase activity and CH/PL ratio. Our results show that administration of α-interferon to CCL-cirrhotic rats improves survival, and liver and erythrocyte membrane function and composition, probably as a result of its antifibrogenic effec

ISSN:0031-7012    

DOI:10.1159/000139163

出版商:S. Karger AG    

年代:1994

数据来源: Karger