摘要:

Glutamate receptors have been identified as important interfaces in learning and memory paradigms as well as in mechanisms of synaptic plasticity, such as long‐term potentiation (LTP) and long‐term depression (LTD), which are believed to be the underlying cellular basis of at least some forms of learning. Although investigations of G‐protein‐coupled receptors have a long history, those depending on ligand‐binding of glutamate have only been discovered recently, and this is the reason why our knowledge about metabotropic glutamate receptors (mGluRs) is at present very limited. However, the development of relatively specific antagonists and agonists has enabled the analysis of the role of mGluRs in synaptic plasticity, mostly studied on the models of LTP and LTD. Among others, we have been able to demonstrate that activation of mGluRs is essential for induction and maintenance of long‐lasting hippocampal LTPin vitroandin vivo. The work conducted by several groups, including ours, has now provided compelling evidence that mGluR activation is an important step in the cellular cascades leading to memory formation in vertebrates. This led us to assume, given that the hippocampus plays a prominent role in spatial rather than discrimination learning, that mGluRs may participate in the processing of spatial information via hippocampal mechanisms, and may thus be similarly important asN‐methyl‐d‐aspartate receptors. This article surveys the literature dealing with mGluRs in hippocampal LTP and learning and memory. We will demonstrate that, although the understanding of cellular mechanisms of neuronal plasticity and of the pharmacology of learning and memory has advanced, the missing link to prove that LTP is a substrate for some forms of learning still remains unsolved. Nevertheless, it appears reasonable to argue that mGluRs in LTP and learning may share some, but not all features, and it will be an interesting approach for further analysis to address the

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.484231000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

cAMP‐induced ion transport in a human sweat gland cell line, NCL‐SG3, was investigated by X‐ray microanalysis and patch‐clamp technique. Stimulation with cAMP caused a decrease in the cellular Cl and K. cAMP had no significant effect on the intracellular Na and Ca. Chloride channel blockers (9‐AC, DPC and NPPB) inhibited the cAMP‐induced chloride efflux. In patch‐clamp experiments the inward current increased over a period of 5–15 min on addition of membrane‐permeable cAMP in 66% of the attempts when the cell was held at 0 mV and pulsed to negative membrane potentials. The inward current was completely blocked by chloride channel blockers. Washout reversed the effect of cAMP. The inward current was not diminished by substitution of impermeable cations for Na in the bath and was insensitive to TEA (tetraethylammoniumchloride). It is concluded that the inward current is mainly a chloride current. Cystic fibrosis transmembrane regulator (CFTR) could not be demonstrated in the NCL‐SG3 cells. It is therefore possible that the chloride efflux is mediated by other types o

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.450223000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

The short‐chain fatty acids acetate, propionate and butyrate induced a concentration‐dependent increase of short‐circuit current (Isc) in the rat distal small intestinein vitro. They were ineffective in the proximal small intestine. The increase ofIscin the distal small intestine was dependent on the presence of Cl‐and HCO‐3ions. It was blocked by the inhibitor of the Na+‐K+‐Cl‐‐cotransporter, bumetanide, and by the Cl‐channel blocker, 5‐nitro‐2‐(3‐phenylpropylamino)‐benzoate, indicating that short‐chain fatty acids evoke an anion secretion. The secretion induced by propionate was blocked by the neurotoxin, tetrodotoxin, and inhibited by the muscarinic antagonists, atropine. In contrast, indomethacin, a cyclooxygenase inhibitor, or nordihydroguaiaretic acid, a lipoxygenase inhibitor, were ineffective. These results indicate that short‐chain fatty acids stimulate chemosensitive neurones in the rat small intestine in a region‐specific manner, which induce anion secretion by

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.470184000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

The free radical spin trap α‐phenyl‐N‐tert‐butyl nitrone (PBN) has previously been shown markedly to reduce infarct size in permanent or transient focal ischaemia in rats. The mechanisms of action have not been clearly defined, but data obtained in focal ischaemia suggest microvessels or mitochondria as targets. Since microvascular dysfunction and/or mitochondrial failure are probably not the immediate causes of delayed neuronal damage following forebrain ischaemia in rats, we induced 15 min of two‐vessel occlusion ischaemia in anaesthetized rats, and assessed brain damage by histopathological techniques 7 days later. Animals were treated either before (30 min) or after ischaemia (30 min or 6 h) with PBN or its vehicle. Other animals received a more soluble PBN analogue (2′‐sulfonyl PBN), and received the drug 30 min prior to 12 or 15 min of ischaemia.PBN reduced neuronal necrosis in the neocortex when given 30 min post‐treatment, but not when given before or 6 h after ischaemia, and it failed to reduce damage to the CA 1 sector of the hippocampus, or the caudoputamen. The sulphonyl derivative of PBN failed to reduce damage in any region.The results provide important hints as to the action of PBN. It is tentatively concluded that the nitrones ameliorate either the microvascular dysfunction or the mitochondrial failure, which could be the crucial events leading to infarction in focal ischaemia, but that they have only a weak effect on the mechanisms that yield selective neuronal necrosis in transient ischaemia o

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.440167000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

The influence of naloxone‐induced general opiate receptor blockade on hypothalamic blood flow autoregulation was investigated in anaesthetized, artificially ventilated, temperature controlled cats. In order to study the changes of the hypothalamic blood flow (H2‐gas clearance technique) at the lower limit of autoregulation systemic arterial pressure was reduced in a stepwise manner to 100, 80, 60 and 40 mmHg, by haemorrhage. Autoregulatory mechanisms of the hypothalamic vessels remained effective and hypothalamic blood flow showed no significant reduction until the arterial pressure was reduced to 60 mmHg in the vehicle‐treated control cats. General opiate receptor blockade by 1 mg kg‐1mL‐1i.v. injected naloxone resulted in a significant reduction of the autoregulatory capacity of the hypothalamic vessels: the blood flow followed passively the arterial pressure fall already from 100 mmHg mean arterial pressure. The effect of opiate receptor blockade on the upper limit of the autoregulation was studied during acute arterial hypertension, induced by angiotensin‐II infusion (25 μg 0.1 mL‐1min‐1i.v.). Hypothalamic blood flow remained remarkably steady following angiotensin‐II infusion in the saline‐treated control animals. Naloxone pretreatment (1 mg kg‐1mL‐1i.v.), however, induced a significant downward shift of the upper limit of the autoregulation, and hypothalamic blood flow started to increase in the 125–145 mmHg arterial pressure range. The narrowing of the autoregulatory range following general opiate receptor blockade suggests an important role of endogenous opioid peptides in hypothalamic blood flow autoregulatory mechanisms both in hypotensive and

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.d01-723.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Force‐generating capacity and electromyographic (EMG) activity of the knee extensor muscles were studied before and after short‐term (10 d) unilateral lower limb unloading and during 4 days of recovery. Ten healthy males used crutches to prevent one of their lower limbs from weight‐bearing while maintaining joint mobility as well as daily ambulatory activities. Knee extensor torque and quadriceps rectified EMG during maximal voluntary isometric contraction (MVC) was measured repeatedly before and after the intervention. Also, EMG at a fixed submaximal level (100 Nm; 30–45% MVC) and maximal angular velocity (AVmax), during unresisted knee extension, were assessed. Maximum torque decreased (P<0.05) by 13±8% in response to unloading while maximum EMG activity did not change after unloading or during recovery (P=0.35). Submaximum EMG increased (P<0.05) by 25±16% after unloading. Maximum and submaximum torque/EMG ratios decreased (P<0.05) after unloading. AVmaxdecreased (P0.05) after 4 days of resumed weight‐bearing. The pronounced decrease and the rapid recovery in maximum torque appears not to be attributed to a change in muscle mass alone. Because the findings of unchanged maximum EMG and increased EMG at a submaximal force level suggest no change in neural drive, we propose that unspecific tissue factors in part impair muscle function in response to short‐term loss of weight‐bearing activity. Results also indicate that recovery in muscle function after short‐term unloading seems to be completed in a time span shorter than the period of

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.476217000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

To test the effect of cooling on EMG‐activity of muscles working as an agonist and antagonist in the lower leg, 12 men dressed in shorts and jogging shoes performed a drop‐jump exercise after 60 min exposures to 27 °C and 10 °C. Cooling decreased mean skin temperature 5.6±0.4 °C (mean±SD,P<0.001), whereas rectal temperature was unaffected. The muscle temperature measured fromm. gastrocnemius medialisdecreased 4.1±0.3 °C (P<0.01) at the depth of 30 mm below skin surface. To find the optimal stretching velocity for potentiation of elastic energy, the drop‐jump exercise was performed from six different bench heights (10, 20, 30, 40, 50 and 60 cm). The optimal velocity was not altered on account of cooling. In cooled subjects during the stretch phase of the drop jumps the EMG‐activity ofm. triceps suraecomplex (agonist) increased (P<0.05–0.001) while the activity ofm. tibialis anterior(antagonist) remained unchanged. After cooling during the shortening phase of the jumps the EMG‐activity ofm. triceps suraecomplex decreased (P<0.05–0.001), whereas the activity ofm. tibialis anteriorincreased (P<0.05–0.001). In addition, after cooling the peak EMG‐activity appeared on the average 28 ms earlier, which shifted the peak activity from the shortening phase (at 27 °C) to the stretch phase (at 10 °C). Cooling increased the mean duration of stretch and shortening phases by 28±3 ms (P<0.001) and 23±2 ms (P<0.001), respectively. The average force production during the shortening phase was 26% less (P<0.05) after cooling, which resulted in a decreased rise of body centre of gravity (P<0.05–0.01). It is concluded that during a stretch‐shortening cycle cooling alters the EMG‐activity of agonist and antagonist muscles on a contradictory manner and results in an earlier peak EMG‐activity. Therefore, alterations in motor unit recruitment could be responsible for the prolonged muscle contraction and decreased fo

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.452172000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

The ageing process is known to be associated with biochemical and functional changes in the heart. In an attempt to determine whether the ability of the coronary endothelium to secrete nitric oxide (NO) both at rest and in response to pharmacological stimulation is age dependent, we studied four groups of rats of different ages (1, 5, 15 and 26 months, respectively). Basal release of NO by endothelium as assessed by response of coronary flow tol‐monomethylarginine, an inhibitor of NO synthase, was higher in the younger age groups. Similarly, the response of coronary flow to 5‐hydroxytryptamine, a selective probe of endothelial capacity to secrete NO, was diminished in the older animals. This was confirmed by direct measurement of NO by chemiluminescence in the coronary effluent. In contrast, the response to glyceryl trinitrate appeared to be unaltered by age. It is concluded that in rats, basal and stimulated release of nitric oxide by the coronary endothelium deteriorates with

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.451171000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

The present study aimed to determine whether vasoconstriction in active calf occurring during combined exercise diminished or persisted when added low‐ and high‐intensity elbow flexion exercise ceased and single leg exercise continued. Six active women (mean age, 21.2 years) participated in this study. During 10‐min plantar flexion exercise at 10% of maximum voluntary contraction (MVC), elbow flexion exercise at 10% MVC was added over the 3rd and 4th min. Calf blood flow did not change significantly upon superimposition and cessation of this elbow flexion exercise. However, when elbow flexion exercise at 50% MVC was added during the 7th and 8th min, calf blood flow above the resting value (2.23±0.23 mL 100 mL‐1min‐1) decreased significantly (P<0.05) from 6.72±0.87 (6th min) to 5.14±1.36 mL 100 mL‐1min‐1after 2 min of combined exercise and was accompanied by a similar change in the non‐exercising calf blood flow value. The vascular conductance of the exercising calf decreased significantly (P<0.01) from 6.48±1.08 (6th min) to 3.11±1.27 mL 100 mL‐1min‐1mmHg‐1at the end of the 2nd min of combined plantar flexion exercise with elbow flexion exercise at 50% MVC. After elbow flexion exercise at 50% MVC was discontinued and plantar flexion exercise at 10% MVC alone was performed, the vascular conductance in the exercising calf remained significantly low for the next 2 min. These results indicate that the vasoconstriction induced by adding high‐intensity arm exercise is persistent, suggesting a major contribution of metabo‐receptor‐mediated vasoconstriction rather than central command‐ and mechano

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.475220000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Bladder growth was induced by partial urethral obstruction. Bladder hypertrophy was evident at 53 h after obstruction and continued over a 6 weeks period. Small bladder arteries were taken from fixed anatomical locations of the bladder circulation, mounted in a small vessel myograph and the optimal diameter for maximal isometric force development was determined (Lmax,K+=125 mmstimulation). Bladder hypertrophy was associated with an enlargedLmaxfrom 53 h onward (compared with sham‐operated controls) andLmaxcontinued to increase until 10 days after urethral obstruction. Between 10 days and 6 weeks no further increase of the diameter was observed. Increased diametersin vitrowere accompanied by a transiently increased [3H]Thymidine uptake in the small arteries which peaked at 53 h after obstruction but was still above background at 10 days. At this time point, small arterial growth was associated with a significant relative increase in the M isoform of LDH as determined with agarose electrophoresis on tissue homogenates. Thus organ growth induced small vessel growth in the rat is characterized by a rapid onset, increased but transient DNA‐turnover and LDH‐isoform changes. The latter mimic changes seen in other types of smooth muscle g

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.458175000.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY