摘要:

Neurotransmitter release from transmitter storage vesicles is a regulated signalling event that has properties in common with other secretory systems. Biochemical characterization of mammalian synaptic vesicle proteins has recently converged with studies of protein traffic in non‐neuronal cells and the genetic dissection of the yeast secretory pathway to give us a considerable amount of new data. Many new synaptic vesicle proteins have been characterized together with plasma membrane proteins with which they interact, and it appears that many of the participating components may be part of a general machinery for secretion. The new results significantly improve our understanding of the molecular mechanisms governing transmitter release. This review discusses the recent progress in terms of synaptic vesicle components and the proposed mechanisms for exocytosi

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1995.tb09880.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

It has previously been shown that caffeine, in a dose‐dependent manner, increases the expression of the protooncogene c‐fos in the rat brain, predominantly in the caudate‐putamen and tuberculum olfactorium. In this study we examined the effect of related xanthines and of selective phosphodiesterase inhibitors on c‐fos expression. The effect of caffeine (75 mg kg1) was mimicked by 3‐isobutyl‐l‐methyl xanthine (IBMX) (25 mg kg‐1) and theophylline (100 mg kg‐1) but not by 8‐p‐sulfophenyltheophylline (10mgkg1), enprofylline, theobromine or paraxanthine (each at 100mgkg1). Moreover, the cyclic AMP‐selective phosphodiesterase inhibitors rolipram (10 or 20mgkg_1) and SQ 20006 (25 mg kg:) and the cyclic GMP‐selective phosphodiesterase inhibitor zaprinast (10 mg kg‐1) failed to induce c‐fos in striatum, but caused a clear‐cut induction in the overlying cerebral cortex. Thus, c‐fos is induced in rat striatum following adminstration of caffeine and other xanthines that (provided they enter the brain) block adenosine receptors, suggesting an involvement of central adenosine receptors. Inhibition of cyclic nucleotide phosphodiesterase does not appear to play any important role in

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1995.tb09881.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

In cerebellar granuleCellcultures, glutamate and N‐methyl‐D‐aspartate (NMDA) caused either neurotoxic or trophic effects, depending on the developmental stage of the neurones. Ethanol (100 mM) partly inhibited delayed neurotoxicity induced by the excitatory amino acids (25μM glutamate for 15 min or 100/tM NMDA for 30 min) assessed 24 h after the incubations in mature cultures in the absence of Mg2t. Glycine (5 μM) potentiated the toxicity of glutamate and the ethanol inhibition, and was routinely added in these experiments. The viability of neurones in the presence of 25 mM K+and 0.8 mM Mg2twas not impaired when maintained in 40–50 mM ethanol for the whole culture period of 7 days. However, ethanol almost completely inhibited the trophic effects of NMDA on developing cultures in 12.5 mM Kμ0.8 mM Mg2+medium. Glutamate (25 μM) and NMDA (100μM) potently induced45Ca2+uptake by granule cells from day 2 in vitro onward. Sixty‐five per cent of the 15‐min45Ca2finflux induced by glutamate and 80% of that induced by NMDA were inhibited by ethanol (100 mM). MK‐801 (a non‐competitive antagonist of NMDA receptors; 100 nM) completely inhibited the toxic and trophic actions of glutamate and NMDA, as well as the45Ca2+influx induced by NMDA, but only 80% of the45Ca2finflux induced by glutamate. These results show that the toxic and trophic actions of glutamate are mediated mainly by Ca2+influx through NMDA receptors. Both of these actions and the underlying Ca2+influx are significantly inhibited by ethanol at pharmacological concentrations (<100 mM), although the mechanisms of inhibition stil

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1995.tb09882.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

To understand the secretion and synthesis of atrial natriuretic peptide we measured immunoreactive atrial natriuretic peptide from plasma, heart tissues and brain areas, and ANP mRNA was determined from heart auricles and ventricles of vasopressin‐deficient Brattleboro rats (DI) and from desmopressin treated Brattleboro rats (DI + DDAVP). Long‐Evans rats (LE) served as controls. DI + DDAVP rats were given for 3 days sc. injections of 0.5/g l‐desamino‐8‐D‐arginine vasopressin in 1 ml. saline twice a day. The rats were housed in single metabolic cages and urinary output and water intake were measured daily. All the body and organ weight parameters were similar in the three groups when the rats were killed. No change was seen in the plasma ANP level between the groups. The right ventricle of DI + DDAVP rats had significantly (P<0.05) higher concentration of ANP than LE rats (15.8 + 4.4 vs. 3.4 + 0.6 ng mg“1tissue). The left ventricle of DI and DI+DDAVP had significantly (P<0.05) lower amounts of ANP mRNA than LE rats (0.5 ± 0.2 vs. 1.3 + 0.2 and 0.5 + 0.1 vs. 1.3 + 0.2 arbitrary units). In the hypothalamus, the ANP concentration was significantly (P<0.05) lower both in DI and in DI + DDAVP rats than in LE rats (9.3 ±1.3 vs. 14.5 ±±1.6 and 6.1+0.6 vs. 14.5 ± 1.6 pg mg‐1tissue).To conclude, although the water intake and urinary output of DI rats were changed towards normal with desmopressin treatment, the heart ventricular and hypothalamic ANP did not parallel the change. Desmopressin increased the ANP concentration in the right ventricle of DI rats. Thus the correction of the complete vasopressin deficiency‐does not appear to associate with synthesis or release of atrial natriuretic peptide in

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1995.tb09883.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The effect of unilateral sympathetic denervation and reinnervation of the lung on a variety of circulatory parameters was investigated in urethane‐anaesthetized rats. The left main stem bronchus together with its surrounding nerves was cut and reanastomosed in 40 rats: 12 intact rats served as controls. Final experiments were performed after 0 days to 10 months: the left stellate ganglion was stimulated. The effect was greatest at 20 Hz. Pulmonary arterial pressure increased significantly (P<0.05) by 10% and pulmonary flow decreased significantly (P<0.05) by 16% in the control rats; no effect on these parameters was found in acutely denervated rats. The stimulus‐elicited change in pulmonary arterial pressure reappeared 1 week after unilateral hilar stripping and gradually returned during reinnervation. After 10 months, the increase in pressure was significantly (P<0.05) larger than that of the control by 50%, whereas the noradrenaline content of the reinnervated lung was significantly (P<0.05) smaller than that of the intact side by 48%. This discrepancy may reflect denervation hypersensitivity of vascular muscle cells. The operations had no effect on systemic circulation: heart rate and systemic arterial pressure increased and aortic blood flow decreased to the same extent in all experimental groups during nerve stimulation. These results suggest that sympathetic reinnervation of the rat lung starts within 1 week but that reinnervation is still incomplete 10 months after unilateral hilar stripp

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1995.tb09884.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

To study the exercise‐induced changes in atrial natriuretic peptide (ANP), a hormone with cardiovascular and renal effects, an incremental submaximal exercise test on a highspeed treadmill was carried out with Standardbred and Finnhorse trotters, the former bred for speed and the latter originally for heavy work. Standardbreds performed the 2 min exercise intervals at speeds of 6, 7, 8, 9 m s‐1and Finnhorses, according to their training status, at 5, 6, 7, 8 m s_1, 4, 5, 6, 7 m s‐1or 5, 6, 7 m s‐1Steady‐state heart rate (HR) was reached within each 2 min interval. The increase in HR was linear and proportional to work intensity and physical condition and it peaked, average 204 beats min‐1, during the last speed of the treadmill. Plasma ANP increased significantly and equally, by 27 + 4 pg mL in both breeds and peaked at 5 min post‐exercise. The rise in ANP during exercise showed good linearity with HR and increasing work intensity. The decrease of ANP after exercise was slow, which may be connected to the regulation of water and electrolytes. Interbreed differences in plasma ANP were not observed. The results suggest a role of ANP in cardiovascular control and fluid balance during and after exercise. In addition to other possible releasing factors during exercise, the increase in HR explains about 40% of the variability in the plas

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1995.tb09885.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Calcium release activity of sarcoplasmic reticulum and enzyme‐histochemical properties were investigated in extensor digitorum longus (e.d.l.) and soleus muscles in young (4 months) and old (24 months) male rats. With age, the caffeine threshold concentration for calcium release from the sarcoplasmic reticulum of soleus skinned muscle fibres showed only minor modifications. On the other hand, in e.d.l. skinned muscle fibres, the caffeine threshold concentration decreased significantly (P<0.05). The histochemical fibre type composition changed with age both in soleus and in e.d.l. muscles, showing a common transformation toward a more oxidative histochemical profile. In fact, in aged soleus, a significant (P<0.05) increase was observed of type 1 fibres to represent almost the totality of the muscle fibres (more than 98%), while types 2C and 2A were reduced in proportion. In aged e.d.l. the percentage of type 1 (P<0.05), 2A and 2X (a recently identified fourth component of the fast‐twitch muscle types) fibres increased, with a reduction of type 2B (P<0.01) fibres. The present results suggest that the changes in contractile properties of aged muscles may be related to the changes not only in fibre composition but also in the mechanism of calcium release from sarcoplasmic reticu

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1995.tb09886.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The role of glucose metabolism and phosphoinositide hydrolysis in glucose‐induced sensitization/desensitization of insulin secretion was studied. A change in glucose concentration from 5.5 to 16.7 mM during 22–24 h of pre‐exposure of mouse islets in TCM 199 culture medium (0.26 mM Ca2+) led to sensitization of glucose‐induced insulin secretion. This change in islet responsiveness to glucose was not mediated by increases in glucose utilization ([5‐3H]glucose conversion to3H20) and glucose oxidation ([U‐14C]glucose oxidation to14C02). Glucose‐induced sensitization of insulin secretion was associated with an increase in glucose‐induced phosphoinositide hydrolysis, leading to a significant increase in inositol 1‐monophosphate formation, but not in inositol 1,4‐bisphosphate or in inositol 1,4,5‐trisphosphate plus inositol 1,3,4‐trisphosphate formation. Diacylglycerol, which may arise from both phosphoinositide hydrolysis and de novo from glucose metabolism, was, on the other hand, not increased during acute exposure to glucose and not changed after pre‐exposure to glucose. At 16.7 mM glucose in TCM 199 medium, a change in Ca2+concentration from 0.26 to 1.26 mM led to a reduction in glucose‐induced insulin secretion. This Ca2+‐dependent desensitization of insulin secretion in the presence of glucose was associated with a decrease in glucose‐induced phosphoinositide hydrolysis, but not with a change in glucose metabolism or diacylglycerol accumulation. In conclusion, it is suggested that glucose‐induced sensitization/desensitization of insulin secretion may involve changes in phosphoinositide hydrolysis, but may occur independently of concomitant changes in glucose metaboli

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1995.tb09887.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Early postnatal sleep‐wake behaviour of male and female rats of Alko Alcohol and Wistar strain was studied using a static charge sensitive mattress when the rats were aged 1 and 2 weeks postnatally. In both strains and sexes, waking time relative to total recording time increased, proportion of quiet state did not change, and that of active sleep decreased during the second postnatal week. The number of long active sleep stages relative to short active sleep stages and the duration of sleep‐wake stages increased with age. Transitions between quiet state and active sleep became fewer with increasing age. Waking time increased more in Wistar rats than in Alko Alcohol rats. At 1–2 weeks of age, the percentage of active sleep and the number of long active sleep stages relative to short active sleep stages were larger, and the duration of sleep‐wake stages longer in Alko Alcohol than in Wistar rats. Sleep‐wake behaviour did not differ between the sexes of either strain or age. Selective breeding for high alcohol preference in Alko Alcohol rats may have caused a genetic trait in early postnatal sleep‐wak

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1995.tb09888.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1995.tb09889.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY