摘要:

Muscarinic cholinoceptor subtypes (M1 and M2) were studied in membrane particles of the rat frontoparietal cortex 72 h and 1, 2, 3, and 4 weeks after ipsilateral lesioning of the nucleus basalis magnocellularis (NBM). The affinity of the ligand used to characterize muscarinic cholinoceptors, 3H-quinuclidinyl benzilate did not significantly change in lesioned compared with sham-operated rats as well as the density of high affinity (Ml) sites. Low affinity muscarinic cholinoceptors (M2 sites) were significantly decreased in NBM-lesioned rats 72 h and 1 week after lesioning. The density of M2 sites did not significantly differ in lesioned rats 2 or 3 weeks after NBM lesioning, but increased, in comparison with sham-operation 4 weeks after NBM lesioning. These findings suggest that frontoparietal M2 muscarinic cholinoceptors, which probably have a presynaptic localization, are sensitive to NBM lesions. Their changes at different times after NBM lesioning suggest the occurrence of loss, compensation and upregulation of cholinergic projections arising to the neocortex from the NBM.

ISSN:0031-7012    

DOI:10.1159/000139060

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The antagonism of carbachol-induced contractions of guinea pig gallbladder smooth muscle strips via selective antagonists, methoctramine, HHSiD, pf-HHSiD and DABDMA has been investigated in order to find out the m-cholinoceptor subtype(s) of gallbladder smooth muscle. All m-cholinoceptor antagonists examined, displaced the concentration-response curves to the right parallel in a concentration-dependent manner without affecting the maximum response. Schild analysis of data was consistent with competitive antagonism, –log KB values of the antagonists were 7.37 for HHSiD, 7.53 for pf-HHSiD, 6.58 for DABDMA and 7.60 for methoctramine. These results, together with the high affinity of pirenzepine and low affinities of 4-DAMP and AF-DX 116, indicate that the m-cholinoceptors of the guinea pig gallbladder which mediate cholinergic contractions are not of m1-, m2- and m3-subtypes but seem likely to be of m4-subtyp

ISSN:0031-7012    

DOI:10.1159/000139061

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

We examined the effect of the potent and selective GABA-B agonists, baclofen, 3-aminopropylphosphinic acid (3-APPi) and 3-aminopropyl (methyl) phosphinic acid (SKF 97541), and the GABA-B antagonists, 3-aminopropyl (diethoxymethyl) phosphinic acid (CGP 35348), 2-hydroxysaclofen and 3-aminopropylphosphonic acid (3-APPA) on cholinergic and peptidergic contractile responses in the airways of guinea pigs. Electrical field stimulation of the isolated guinea pig trachea produced cholinergic contractions that were inibited by baclofen (EC50 = 5 μmol/l), 3-APPi (EC50 = 0.3 μmol/l) and SKF 97541 (EC50= 0.4 μmol/l). The inhibition by baclofen (30 μmol/l) was reduced by CGP 35348 (IC50 = 65 μmol/l), 2-hydroxysaclofen (IC50 = 273 μmol/l) and 3-APPA (IC50 = 355 μmol/l). The in vivo cholinergic bronchoconstrictor response to vagal nerve stimulation (5 V, 20 Hz, 0.5 ms for 5 s) was attenuated by intravenous baclofen (ED50 = 1.7 mg/kg), 3-APPi (ED50 = 0.9 mg/kg) and SKF 97541 (ED50 = 0.2 mg/kg). The inhibition of vagally induced bronchoconstriction by baclofen was blocked by CGP 35348 (1-10 mg/kg, i.v.) and 2-hydroxysaclofen (10 mg/kg, i.v.). A cholinergic bronchoconstriction induced by CNS stimulation (400 μA, 2 ms, 32 Hz for 5 s) was inhibited by baclofen (ED50 = 5.1 mg/kg, i.v.) and 3-APPi (ED50 = 0.6 mg/kg, i.v.). The effect of baclofen was attenuated by 3-APPA (5 mg/kg, i.v.). A peptidergic bronchoconstriction was evoked by intravenous nicotine (1 mg/kg) in animals treated with ipratropium and phosphoramidon. This bronchoconstriction was inhibited by baclofen (ED50 = 1.2 mg/kg, i.v.) and 3-APPi (ED50 = 0.6 mg/kg, i.v.), and the effect of baclofen was attenuated by 3-APPA (5 mg/ kg, i.v.). Therefore, a GABA-B receptor-mediated inhibition of neurally induced cholinergic and peptidergic airway constriction was demonstrated by using baclofen and the newer GABA-B agonists, 3-APPi and SKF 97541. The effects of baclofen were reduced by GABA-B antagonists including CGP 35348, the most potent antagonist available. These results support the hypothesis that a peripheral GABA-B receptor is an inhibitory neuromodulator in the

ISSN:0031-7012    

DOI:10.1159/000139062

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The mitochondria harvested at the end of perfusion of control hearts and assayed for respiratory activity had a better function after ischemia and reperfusion following trimetazidine injection when glutamate was used as substrate. The protective effect of trimetazidine was enhanced when the mitochondria were isolated from hypertrophied perfused rat hearts. In fact the drug improved both the RCI and QO2 parameters with glutamate or succinate as substrates and raised the glutamate-induced QO2 value of mitochondria extracted from the hypertrophied heart perfused in aerobic conditions. In the aerobically perfused heart trimetazidine did not change either the levels of tissue malondialdehyde and lipofuscin, or the rate of mitochondrial O2· generation while it reduced the O2· formation and malondialdehyde content in the hypertrophied heart. After ischemia and reperfusion, the drug reproduced these protective effects in the hypertrophied hearts and reduced the level of tissue malondialdehyde in control hearts. The protective effect of trimetazidine against MDA formation was dose-dependent, being more evident at a higher dose (10 μmol/l). Preincubation of rat heart mitochondria with 0.1–10 μmol/l trimetazidine did not affect NADH oxidase, NADH dehydrogenase and NADH-cytochrome c reductase, succinate oxidase and cytochrome c oxidase activities. These results indicate that trimetazidine injected into isolated rat hearts protects against the damage induced on cardiac energetics and oxidative injuries by moderate ischemia and reperfusion stress, particularly in monocrotaline-induced hypertrophy in the rat heart. We suggest that trimetazidine reduces the formation of oxidative damage by preserving cardiac mitochondrial fun

ISSN:0031-7012    

DOI:10.1159/000139070

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The present investigation was designed to extend our previous observations that α-methyl-p-tyrosine (AMPT; an inhibitor of norepinephrine synthesis) reduced splenic natural killer (NK) cell activity and to test whether NK augmentation or augmenting interferon (IFN) production induced by polyriboinosinic acid:polyribocytidylic acid (poly I:C; an IFN inducer) can be attenuated by AMPT in mice. Therefore, in the current study, the effects of AMPT (300 mg/kg i.p.) on splenic NK activity or plasma titers of IFN-α+β were assessed in inbred C57BL/6 mice. It was found that treatment with AMPT reduced both poly I:C induced serum IFN and splenic NK activity in a dose-and time-dependent manner. These results suggest that AMPT inhibits IFN production and decreases splenic NK activity in vi

ISSN:0031-7012    

DOI:10.1159/000139063

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Added to human serum in vitro, RU 41740, an immunomodulating agent extracted from Klebsiella pneumoniae, binds selectively to lipoproteins containing apolipoprotein B (low-density lipoproteins and very-low-density lipoproteins, VLDL) and, at higher concentrations, to lipoproteins containing apolipoprotein A (high-density lipoproteins). The fact that lipoproteins modulate polymorphonuclear neutrophil (PMN) functions led us to suspect that the VLDL-RU 41740 complex might affect PMN functions. In this study, the effect of this complex on PMN superoxide generation was measured in the presence and absence of the classical stimulants formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate. The VLDL-RU 41740 complex enhanced the stimulating effect of VLDL on quiescent PMN, but not following stimulation with formyl-methionyl-leucyl-phenylalanine. In contrast, it partially counteracted the inhibiting effect exerted by VLDL alone on phorbol myristate acetate stimulation. Such a complex might be formed in vivo during RU 41740 therapy and constitute an important feature in the immunostimulating properties of the drug.

ISSN:0031-7012    

DOI:10.1159/000139064

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Hyperreflexia, a condition characterized by contractions of the urinary bladder, is not mediated by a micturition reflex. The contractions can be of neurogenic origin through spinal or supraspinal reflexes or of myogenic origin, independent of neuronal mediation. There is a clear relationship between hyperreflexia and symptoms such as urgency, frequency, nocturia and urinary incontinence. Therapies to reduce the presence of uninhibited bladder contractions include oral drug therapy, instillation drug therapy and parasympathetic nerve ablation. The current study characterizes the ability of terodiline to inhibit an experimental form of hyperreflexia and compares the efficacy and potency of terodiline and other agents on hyperreflexia and evoked contractions. The results can be summarized as follows: (1) terodiline inhibits the amplitude of the hyperreflexia at lower concentrations than it inhibits the frequency of hyperreflexia; (2) terodiline had no statistically significant effect on mean blood pressure at any concentration utilized; (3) terodiline had approximately the same potency for inhibition of 2 and 32 Hz stimulation for both the bladder body and base; (4) terodiline inhibited the maximum contractile response to bethanechol and also shifted the curve to the right, demonstrating that terodiline is a mixed inhibitor, and (5) terodiline was a noncompetitive inhibitor of KCI.

ISSN:0031-7012    

DOI:10.1159/000139065

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The NADH/NAD ratio is a measure of potential metabolic energy in smooth muscle tissue. Previous studies on bladder smooth muscle demonstrated that during active contraction when energy utilization is high, NADH is rapidly oxidized to NAD resulting in a decrease in the ratio of NADH/NAD. Intracellular systems utilizing ATP as an energy source are characterized by changes in the NADH/NAD ratio. This ratio can be monitored simultaneously with changes in smooth muscle tissue tone using an optical fiber probe which continually monitors NADH fluorescence and contractile activity of the same smooth muscle preparation. The present study correlates alterations in the ratio of NADH/ NAD with both spontaneous and induced contractions and relaxations in the rabbit corpora cavernosa. The results show a high degree of correlation between a decrease in spontaneous fluorescence (decrease in the NADH/NAD ratio) and spontaneous contraction. An increase in tension was followed in time by a decrease in the NADH/NAD ratio. This was consistent for all strips showing significant spontaneous activity. ATP caused a rapid decrease in tension which was correlated with a decrease in fluorescence. The relative decrease in NADH fluorescence was proportional to the relative decrease in tension. Under basal conditions (0.8 g passive tension) ATP and nitro-prusside stimulated a marked reduction in tension, but only ATP stimulated a substantial decrease in NADH fluorescence. Bethanechol and isoproterenol relaxed the corporal tissue to a relatively small degree which correlated with relatively small decreases in fluorescence. Methoxamine stimulated a substantial contraction of corporal smooth muscle which correlated with a rapid and significant decrease in NADH fluorescence. Following precontraction by methoxamine, ATP stimulated a marked decrease in both tension and fluorescence. Nitroprusside and bethanechol similarly stimulated marked decreases in tension with only minor changes in NADH fluorescence. Isoproterenol induced a minor decrease in tension with no significant change in NADH fluorescence from that of the basal response. The dissociation of the endothelium from the corporal tissue inhibited the response to bethanechol by 90% for both fluorescence and tension while the response to ATP was virtually unaffected. In summary, the data indicate a strong correlation between stimulation of contraction by methoxamine and a decrease in the NADH/NAD ratio; and strong relaxation of corporal smooth muscle by ATP and a decrease in the NADH/NAD ratio. Since these drugs have opposite effects on tension, this result may indicate that both contraction- and ATP-induced relaxation in the rabbit corpus cavernosa are active processes and depend on the rapid utilization of cellular metabolic energy. It appears that corporal relaxation mediated by nitroprusside is highly efficient, utilizing significantly less intracellular energy and producing maximal relaxations.

ISSN:0031-7012    

DOI:10.1159/000139066

出版商:S. Karger AG    

年代:1993

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000139067

出版商:S. Karger AG    

年代:1993

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000139068

出版商:S. Karger AG    

年代:1993

数据来源: Karger