摘要:

SUMMARY1. Disulfiram or related compounds were administered to rats by stomach tube and the activities of alcohol dehydrogenase and aldehyde dehydrogenase in the liver and the gastric mucosa were determined 43 h later.2. In liver, disulfiram did not affect alcohol dehydrogenase activity but reduced aldehyde dehydrogenase activity. The disulfiram metabolite diethyldithiocarbamate was without action.3. In gastric mucosa, disulfiram had no effect on aldehyde dehydrogenase activity but enhanced alcohol dehydrogenase activity. Diethyldithiocarbamate had a similar effect.4. The increase in alcohol dehydrogenase activity in the gastric mucosa might explain the hyperacetaldehydaemia produced by ethanol in disulfiram‐treated patient

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00558.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. The relationship between determinants of membrane potential has been studied during myogenesis in culture.2. Myoblasts obtained from 11‐day chick embryo musculature were cultured and intracellular records were made from myoblasts and developing unstriated and striated myotubes.3. Resting membrane potentials increased with time of culture until values equivalent to those obtained from fully developed striated muscle fibres were reached after about 20 days in culture.4. High concentrations of potassium added to the medium failed to affect significantly the resting membrane potentials in myoblasts and myotubes up to 10 days in culture. Changes in external sodium had little effect on values of potentials from myotubes and cells up to 4 days in culture, but removal of sodium after 5 and 6 days in culture caused depolarization.5. Electrolyte distributions determined for myoblasts and myotubes 4 days after fusion showed no significant change in potassium content, whereas the sodium concentration fell significantly.6. Acetylcholine applied by microinjection caused two types of response from myoblasts depending upon the level of the resting membrane potential: when the potential was less than —7 mV, hyperpolarization occurred; when it was greater than this value, depolarization occurred.7. Depolarizing responses to acetylcholine application were regularly obtained from myotubes with resting membrane potentials greater than —7 mV.8. The responses to acetylcholine could be blocked byd‐tubocurarine in the medium; tetramethylammonium (a nicotinic agonist) acted similarly to acetylcholine, but bethanecol (a muscarinic agonist) had no

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00559.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. Intracerebroventricular (icv) administration of the renin inhibitor pepstatin inhibited the dipsogenic response to icv renin but did not affect drinking induced by icv angiotensin I and II.2. Intracerebroventricular administration of an angiotensin converting enzyme inhibitor, SQ 20881, reduced the dipsogenic effect of icv renin and angiotensin I but did not affect angiotensin II induced drinking.3. Intracerebroventricular administration of SQ 20881 reduced the dipsogenic effect of intravenous angiotensin I but did not reduce drinking elicited by intravenous angiotensin II.4. Intracerebroventricular administration of Sar1‐Ala8‐angiotensin II, a competitive antagonist of angiotensin II, inhibited drinking elicited by icv renin, angiotensin I and angiotensin II. The dipsogenic response to intravenous infusion of both angiotensins I and II was reduced after central administration of this antagonist.5. Four analogue antagonists of angiotensin II given icv reversibly inhibited the dipsogenic response to icv angiotensin II. These analogues themselves possessed weak dipsogenic effects.6. Renin‐angiotensin induced drinking in the cat is mediated by the action of angiotensin II on receptors in the central nervous s

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00560.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. Serotonin is present in blood vessels and the heart of the rat in concentrations of about one‐sixth that of noradrenaline.2. The concentrations of serotonin are increased two‐fold following treatment with the monoamine oxidase inhibitor, pargyline, and the elevation of levels is rapid.3. It is suggested that monoamine oxidase regulates the content of serotonin in blood vessels and the he

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00561.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. The actions of the sympathomimetic bronchodilator trimetoquinol (AQL 208) have been compared with those of laevoisoprenaline on the cardiac, respiratory and skeletal muscle systems of the cat under chloralose anaesthesia, and on cat isolated atrial and tracheal preparations.2. Trimetoquinol injected intravenously ranged in potency from two to four times less potent to about four times more potent than laevoisoprenaline in differentin vivoexperiments. Despite such wide variations in absolute potency the mean effective doses of trimetoquinol in bothin vitroandin vivostudies were not significantly different (P>0.05) from those of laevoisoprenaline.3. The effect on the soleus muscle is considered to be analogous to the muscle tremor that often occurs in man, and the results suggest that systemic administration of trimetoquinol may produce muscle tremor as an unwanted side effect in some patients.4. Trimetoquinol, in the cat, shows no evidence of the selectivity for β‐adreno‐receptors in different tissues reported for it in other species. It is suggested that β‐receptors in the cat are less clearly differentiated and that they resemble those in man more closely than do those in other

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00562.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. The effects of various compounds on the fluorescence of microsome‐bound 1‐anilino‐8‐naphthalene sulphonate (ANS) have been studied.2. Cationic drugs and divalent metal cations enhance the fluorescence of microsome‐bound ANS whereas anionic drugs and primary aliphatic alcohols decrease it.3. No changes were observed in the fluorescence lifetime or emission maximum of ANS and it was concluded that there were no significant changes in the quantum yield of ANS fluorescence.4. The changes in fluorescence are shown to be related to changes in ANS binding.5. The results suggest that drug‐induced changes in the binding of ANS to the microsomal membrane reflect a change in the net charge on the membrane as a result of the binding of a charged drug and that changes in ANS fluorescence cannot be directly interpreted as changes in the structure of the membrane.6. Primary aliphatic alcohols displace ANS from the microsomal membrane but cause no change in quantum yield. It is suggested that the alcohols change the net charge on the membrane either by exposure of negative charges or occlusion of positive charges.7. The changes in ANS fluorescence can be used as a measure of the interaction of various drugs with the microsomal membrane. Apparent binding constants determined by this method for various drugs fall in the concentration ranges over which the drugs are reported to induce changes in membrane function in variousin v

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00563.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. Desipramine, nortriptyline, amitriptyline, imipramine and cocaine inhibit the uptake of3H‐noradrenaline in isolated guinea‐pig atria. The order of potency is as listed; the concentrations producing 50% inhibition are 0.026, 0.036, 0.193, 0.288 and 3.47 μM, respectively.2. The effects of desipramine and amitriptyline in a range of concentrations (0.01–100 μM) were tested on the resting and stimulation‐induced efflux of radioactivity from isolated guinea‐pig atria in which adrenergic transmitter stores had been labelled with3H‐(‐)‐noradrenaline.3. Stimulation‐induced efflux is slightly enhanced by a low concentration (0.01 μM) of desipramine, but is markedly reduced by concentrations of 30 and 100 μM. With 100 μM, there is a marked increase in resting efflux.4. Amitriptyline enhances stimulation‐induced efflux to a greater extent than does desipramine, and the maximal effect is produced with a higher concentration (30 μM). With 100 μM, stimulation‐induced efflux is not significantly altered from control and resting efflux is increased, but to a lesser extent than with 100 μM desipramine.5. It is concluded that desipramine and amitriptyline exert more than one action on adrenergic transmission: in addition to inhibiting neuronal uptake of noradrenaline, they also release noradrenaline, and desipramine interferes with the release of transmitter in

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00564.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. Sustained‐release formulations of alprenolol and glyceryl trinitrate and placebo preparations were given to twelve patients with angina pectoris, each treatment being given for a 5 day period in a double‐blind cross‐over design. The patients had previously been effectively treated with β‐adrenoreceptor antagonists.2. The effects of treatments on subjective symptoms and on exercise tolerance using a bicycle ergometer were assessed.3. There were no significant differences between the subjective symptoms or the consumption of glyceryl trinitrate on the three treatments.4. Exercise tolerance was significantly higher on alprenolol treatment than when the subjects were on glyceryl trinitrate or placebo treatment.5. In five patients, sustained‐release glyceryl trinitrate treatment increased exercise tolerance. Four of these patients had not previously had a myocardial infarction.6. Ischaemic changes in the ST and T segments during exercise were influenced to the same degree by both active drugs, and were significantly less pronounced than on placebo treatment.7. A compartmentalized container for tablet dispensing, Dosett ®, proved to be useful in ensuring regular treatment according to i

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00565.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. Experiments were performed with preparations obtained by medial transection of the rat vas deferens providing urethral and testicular segments, to determine whether the smooth muscle of this organ responds uniformly along its length to field excitation of sympathetic nerve terminals and to sympathomimetic amines.2. Both preparations responded to pulses applied at 0.1 Hz with twitches which were blocked by guanethidine (1–10 μM) indicating that sympathetic nerve terminals were being stimulated. Xylazine (0.01–1 μM) also blocked the twitches.3. In response to stimulation at 0.1 Hz the twitches of the urethral segment were larger but briefer than those of the testicular segment. However, the increase in tension with increase in stimulation frequency over the range 0.01–10 Hz was greater in the testicular than in the urethral segment. After a train of pulses at 1 Hz or above, the first few twitches of the testicular segment evoked by pulses applied at 0.1 Hz were facilitated, whereas twitches of the urethral segment were inhibited.4. Noradrenaline (1–100 μM) and tyramine (1–100 μM) regularly enhanced twitches in response to stimulation at 0.1 Hz in the testicular segment but often reduced those in the urethral segment. Contractions in response to these amines occurred more regularly and were stronger in the testicular than in the urethral segment. The α‐adrenoreceptor antagonists phenoxybenzamine (0.01 μM), phentolamine (10 μM) and thymoxamine (10 μM) blocked contractions and blocked or reversed the twitch enhancement produced by noradrenaline and tyramine. These observations indicate that the density of excitatory α‐adrenoreceptors is greater at the testicular end of the tissue.6. Twitch inhibition evoked by noradrenaline or by tyramine in urethral segments was resistant to blockade by phenoxybenzamine (0.01 μM), phentolamine 10 μM), thymoxamine (10μM) and propranolol (10 μM).7. A histological comparison of the two ends of the vas deferens indicated that at the urethral end there was more circularly arranged muscle and that this interrupted bundles of longitudinally arranged muscle. The testicular end was thinner but had the higher proportion of longitudinally arranged fibres.8. The differences between the two ends of the vas deferens in the arrangement of muscle layers and in the response to sympathetic nerve stimulation and to drugs may be of physiological significance in relation to the transport of sperm from the

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00566.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. The influence of the anorectic drugs, aminorex, chlorphentermine and phenmetrazine, on the pulmonary vascular system has been studied in the isolated perfused rat lung.2. The drugs did not directly effect the vascular resistance. Aminorex and chlorphentermine prolonged the vasoconstrictive effect of serotonin by an inhibition of its metabolic breakdown. Both drugs inhibited monoamine oxidase and impaired the cellular uptake of serotonin into the lung tissues, resulting in an elevated serotonin level which caused a persisting constriction of the pulmonary vessels.3. Phenmetrazine was without effect on the vasoconstrictor action of serotonin or serotonin metabolism in the isolated rat lung.

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00567.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY