bluuebunny/crossref_metadata_2025_split huggingface dataset:
Copper metabolism during acute inflammation: studies on liver and serum copper concentrations in normal and inflamed rats
Authors: Conforti A. , Franco L. , Milanino R. , Totorizzo A. , Velo G.P. 
Published: July 2012

The concentration of copper in serum and liver was determined by atomic absorption spectrophotometry in a study performed on normal rats of either sex and in female rats with carrageenan‐induced pleurisy.
In the normal animal, total serum copper concentration is significantly higher in female rats, and appears to be higher in mature animals in females.
In normal rats of either sex, liver copper concentration undergoes daily variations which are inversely related to the weight of the organ and which leave constant the total amount of metal in the liver. Moreover a day to day non‐cyclic variability of liver copper concentration and liver weight was observed.
This first set of data showed that comparison with time control was essential.
In the inflamed rat, a significant rise of total serum copper at 22, 48 and 72 h after the induction of inflammation was observed. From 96 h up to 240 h post‐injection no significant differences were evident.
Total liver copper content did not change in the inflamed rats.
During acute inflammation in the rat, the copper needed for the increased synthesis of caeruloplasmin is supplied without depletion of liver copper stores.
The binding of [125I]‐angiotensin to rat renal epithelial cell membranes
Authors: Cox Helen M. , Munday Kenneth A. , Poat Judith A. 
Published: July 2012

Specific high affinity binding sites for [125I]‐angiotensin II have been identified in crude basolateral and brush border membranes from rat renal cortex.
A central high affinity site, KD 0.62 nM; Bmax 299 fmol/mg was identified as part of a complex multicomponent binding system.
This high affinity site was saturable and exhibited specificity for angiotensin II analogues and closely related peptides but not for bradykinin, substance P or peptide fragments of angiotensin II.
Specific [125I]‐angiotensin II binding was partially dependent on NaCl. Absence of NaCl resulted in a decrease in Bmax, had no effect on the rate of association but increased the rate of dissociation of [125I]‐angiotensin from its binding site.
An investigation of the importance of the adrenal gland to the action of dopamine in the rat kidney
Authors: Akpaffiong M.J. , Redfern P.H. , Woodward B. 
Published: July 2012

In the rat, administration of dopamine is associated with diuresis, natriuresis and a decreased excretion of K+. The site of action of dopamine in mediating these responses has been investigated.
Urine volume, and urinary Na+, K+, Cl− and dopamine concentrations have been measured in adrenalectomized and sham‐operated male Wistar rats.
As expected, adrenalectomy decreased urine volume and increased Na+ and Cl− excretion; at the same time the amount of dopamine excreted fell, and K+ excretion did not change.
Administration of either 3% NaCl (20 ml/kg orally) or frusemide (100 mg/kg s.c.) significantly elevated dopamine excretion after adrenalectomy.
When dopamine, 1, 10 and 30 mg/kg (s.c.) was given to adrenalectomized rats, the diuresis and fall in K+ excretion seen in control animals was still present. No further natriuresis, over and above the already high urinary Na+ levels, was observed.
The results show that the three actions of dopamine in inducing diuresis and natriuresis, and decreasing K+ excretion, are clearly separable.
It is further argued that in mediating these effects the main site of action of dopamine is the kidney rather than the adrenal gland.
Influence of extracellular calcium and calcium antagonists on contractions induced by potassium and prostaglandin F2α in isolated cerebral and mesenteric arteries of the cat
Authors: Andersson K.‐E. , Edvinsson L. , MacKenzie E.T. , Skärby T. , Young A.R. 
Published: July 2012

The effects of a number of calcium antagonists (diltiazem, nifedipine, nimodipine and verapamil) have been studied on feline isolated pial arteries contracted by potassium (127 mM) or prostaglandin F2α (PGF2α, 2.5 μM) and mesenteric arteries contracted by potassium (127 mM).
Withdrawal of Ca2+ from the extracellular medium for 30 min reduced the contractile response to potassium in cerebral vessels by 92% and in mesenteric vessels by 96%. Subsequent addition of Ca2+ caused reproducible contractions which were inhibited by both nifedipine and nimodipine.
The four calcium antagonists relaxed the isolated middle cerebral artery contracted either by potassium or PGF2α, and mesenteric arteries contracted by potassium, in the following order of potency: nimodipine > nifedipine > verapamil > diltiazem.
Nimodipine was more potent than nifedipine in cerebral arteries, and more potent in cerebral than in mesenteric arteries. Otherwise, the potassium‐contracted cerebral and mesenteric vessels showed no major differences in sensitivity to calcium antagonists.
A comparison of the effects of morphine, enkephalin, kyotorphin and D‐phenylalanine on rat central neurones
Authors: Stone T.W. 
Published: July 2012

Morphine, Met‐enkephalin, kyotorphin and D‐phenylalanine have been applied by microion‐tophoresis to neurones in the globus pallidus and cerebral cortex of rats anaesthetized with urethane.
In the pallidum, most cells were inhibited by all the agonists, with a high correspondence between cells inhibited by Met‐enkephalin and D‐phenylalanine and by Met‐enkephalin and kyotorphin. Whereas responses to Met‐enkephalin were readily antagonized by naloxone, responses to kyotorphin and D‐phenylalanine were not.
In the cerebral cortex a high proportion of cells was excited by all four agonists and antagonism by naloxone was less consistent than in pallidum.
It is concluded that the naloxone‐reversible analgesic effects of kyotorphin and D‐phenylalanine may be mediated indirectly, rather than through an activation of opiate receptors.
Characterization and partial purification of ‘renocortins’: two polypeptides formed in renal cells causing the anti‐phospholipase‐like action of glucocorticoids
Authors: Cloix Jean François , Colard Odile , Rothhut Bernard , Russo‐Marie Françoise 
Published: July 2012

Anti‐inflammatory steroids reduce prostaglandin E2 (PGE2) synthesis in rat renomedullary interstitial cells in culture by inhibiting the release of arachidonic acid from membranous phospholipid stores, exhibiting antiphospholipase‐like properties.
After treatment of the cells with dexamethasone 10−6M, these cells release a protein in the supernatant.
This supernatant is able to inhibit PGE2 secretion in untreated cells and to inhibit phospholipase A2 activity in an in vitro system.
Using chromatofocusing separation, we showed that two distinct proteins exist with isoelectric points of 5.8 and 8.3.
Using gel permeation separation, we showed that two proteins exist with apparent molecular weights of 15,000 and 30,000 daltons.
We conclude that, in renal cells in culture, anti‐inflammatory steroids induce the synthesis and the release of two polypeptides which we have named ‘Renocortins’ (induced by corticoids in renal cells) causing the antiphospholipase‐like action of glucocorticoids.
Our results are in good agreement with others, but as renal cells are not directly involved in the inflammatory process, we suggest that this steroid‐induced phenomenon is not solely involved in the inflammatory reaction but is of more general physiological relevance.
Comparison of the excitatory actions of substance P, carbachol, histamine and prostaglandin F2α on the smooth muscle of the taenia of the guinea‐pig caecum
Authors: Benham C.D. , Bolton T.B. 
Published: July 2012

A comparison was made of the actions of substance P, prostaglandin F2α (PGF2α), histamine and carbachol on the membrane potential and conductance of the longitudinal smooth muscle of the taenia of the guinea‐pig caecum using the double sucrose gap apparatus.
The increases in conductance produced by the four drugs during matched depolarizations in the sucrose gap were not significantly different and they were substantially larger than the increase in conductance brought about during the same depolarization produced by passing outward current.
In sucrose‐substituted, Na‐ and Cl‐deficient solution the increases in conductance and depolarization due to carbachol, substance P, and PGF2α were attenuated to a similar extent. The depolarization due to histamine under these conditions was reduced to a significantly greater extent than that due to carbachol. In Tris‐benzene‐sulphonate substituted Na‐ and Cl‐deficient solution the responses due to carbachol and histamine were attenuated to a similar extent. This suggests that sucrose addition may have a specific effect on the histamine response.
In Tris‐substituted Na‐deficient solution the increases in conductance and depolarization produced by substance P, histamine and carbachol were attenuated to a similar extent. The depolarization due to PGF2α was reduced by a significantly greater amount which may be due to unmasking an inhibitory effect that was sometimes apparent in normal solution.
In benzenesulphonate‐substituted, Cl‐deficient solution the increases in conductance and depolarizations produced by moderate concentrations of PGF2α, histamine and carbachol were attenuated to a similar extent. The response to substance P was little affected. In glucuronate‐substituted, Cl‐deficient solution the increases in conductance and depolarizations due to substance P and carbachol were attenuated to a similar extent. This result, and the observation that the depolarization to large concentrations of carbachol was not reduced in benzenesulphonate‐substituted, Cl‐deficient solution, suggest that benzenesulphonate interferes with the reactions of the non‐peptide stimulants with their respective receptors.
The similarities in the effects of activating the four types of receptor under some conditions could be explained if they all acted on the same population of receptor‐operated channels. In addition it seems that PGF2α acts also on a population of inhibitory receptors, sucrose interferes with histamine's action, and benzenesulphonate interferes with the reactions of non‐peptide stimulants with their respective receptors.
The effect of bilateral adrenal demedullation on vascular reactivity and blood pressure in spontaneously hypertensive rats
Authors: Borkowski K.R. , Quinn P. 
Published: July 2012

Bilateral adrenal demedullation of juvenile spontaneously hypertensive rats attenuated, but did not prevent, the development of hypertension. Neither did it affect the subsequent vascular reactivity to phenylephrine though it significantly reduced the vascular effects of sympathetic nerve stimulation.
Demedullation of adult spontaneously hypertensive rats did not alter blood pressure, but did attenuate the pressor responses to both α‐adrenoceptor agonists and sympathetic nerve stimulation.
In acutely demedullated adult rats, vascular reactivity to sympathetic nerve stimulation, but not to exogenous amines, could be restored by slow i.v. infusion of adrenaline in a dose‐dependent manner.
The results support a possible facilitatory role for adrenaline in sympathetic neurotransmitter release, both during the development of genetic hypertension and in vascular responses to sympathetic nerve stimulation.
Functional interactions of calcium‐antagonists in K+‐depolarized smooth muscle
Authors: Spedding Michael 
Published: July 2012

The functional significance of the interaction of certain calcium‐antagonists with nimodipine was examined so that this might be related to binding studies. To this end, the relaxant effects of nimodipine (1–100 nm) on Ca2+ (10 mm) ‐induced contractions of K+‐depolarized taenia preparations from the guinea‐pig caecum were compared in the presence of nifedipine and cinnarizine (which competitively displace [3H]‐nimodipine with high and low affinities respectively), diltiazem (which increases binding), verapamil (which allosterically reduces binding) and W‐7, a calmodulin antagonist.
The relaxant effects of nimodipine were similar in the presence of nifedipine, diltiazem and cinnarizine, but were slightly attenuated in the presence of verapamil and W‐7.
These findings can be reconciled with the differentiation of calcium antagonists evident from [3H]‐nimodipine binding studies, but indicate that the functional consequences of allosteric interactions disclosed in such studies are small. Drugs which bind to calcium channels and drugs which bind to calmodulin did not potentiate each other.
Responses of human skin to intradermal injection of leukotrienes C4, D4 and B4
Authors: Camp R.D.R. , Coutts A.A. , GreavesM M.W. , Kay A.B. , Walport M.J. 
Published: July 2012

The ability of intradermally injected leukotrienes C4 (LTC4), LTD4 and LTB4 to produce inflammatory changes in human skin alone and in combination with prostaglandin E2 (PGE2) has been investigated.
LTC4 and D4 (0.012–0.38 nmol) caused dose‐related erythema and wealing. No evidence of synergism between PGE2 and LTC4 or LTD4 was detected, although only single dose combinations were studied.
LTB4 (0.15–1.5 nmol) caused areas of induration which persisted for more than 4 h and which showed perivascular neutrophil infiltrates on histological examination. Only slight synergism between PGE2 and LTB4 was found.
It was concluded that these pro‐inflammatory properties of LTC4, LTD4 and LTB4 are consistent with their proposed roles as mediators of inflammation in the skin and other tissues.
The inhibitory effects of N2‐dansyl‐l‐arginine‐4‐t‐butylpiperidine amide (TI 233) on contraction of vascular and intestinal smooth muscle
Authors: Karaki H. , Murakami K. , Nakagawa H. , Urakawa N. 
Published: July 2012

Effects of N2‐dansyl‐l‐arginine‐4‐t‐butylpiperidine amide (TI 233) on the contractions in vascular and intestinal smooth muscles were examined.
High K‐induced sustained contractions in the smooth muscles were inhibited by TI 233 with an IC50 of 2.1 × 10−5m for rabbit aorta and 3.6 × 10−6m for guinea‐pig taenia coli in a solution containing 1.5 mm Ca. Initial transient contraction induced by K in taenia coli was less sensitive to the inhibitory effect of TI 233. When the Ca concentration in the medium was decreased to 0.3 mm, the concentration‐inhibition curves for TI 233 shifted to the left in both aorta and taenia coli. Increasing the Ca concentration to 7.5 mm shifted the curve to the right in the aorta. TI 233 also inhibited the noradrenaline‐induced contraction in the aorta (IC50 = 2.1 × 10−5 m).
In a hypoxic solution without added glucose, the inhibitory effect of TI 233 on the K‐induced contraction in aorta was augmented. In the presence of high concentrations (40 mm) of glucose in hypoxia, TI 233 did not inhibit the noradrenaline‐induced contraction of the aorta. Hypoxia and a high concentration of glucose also decreased the inhibitory effect of TI 233 on the K‐induced contraction in taenia coli.
TI 233 inhibited the K‐induced increase in cellular Ca content measured by a modified lanthanum method.
TI 233 decreased oxygen consumption and ATP content of resting and K‐stimulated aorta and taenia coli.
It was concluded that TI 233 inhibits the vascular and intestinal smooth muscle contraction by a Ca antagonistic action and also by inhibition of aerobic metabolism.
Separation of adrenergic and non‐adrenergic contractions to field stimulation in the rat vas deferens
Authors: Brown D. A. , Docherty J.R. , French A.M. , MacDonald A. , McGrath J.C. , Scott N.C. 
Published: July 2012

Adrenergic and ‘non‐adrenergic’ nerve‐induced contractions in rat vas deferens were separated pharmacologically.
Responses to single stimuli comprised two components, an α‐noradrenergic component (IIs), dominant in the epididymal portion, and a ‘non‐adrenergic’ component (Is), dominant in the prostatic portion. Is but not IIs was blocked by nifedipine. A combination of adrenergic blockade and nifedipine virtually abolished all components. After cocaine, a third component (IIIs) emerged which was abolished by either adrenergic blockade or nifedipine.
The response to trains of stimuli consisted of ‘twitch’ and ‘secondary’ components. This biphasic time course was modified by adrenergic blockade or nifedipine to reveal the time course of the ‘non‐adrenergic’ and adrenergic components, respectively: these did not correspond to the ‘twitch’ and ‘secondary’ components. A combination of adrenergic blockade and nifedipine virtually abolished the whole response.
Prejunctional α2‐adrenoceptor‐mediated inhibition of the contractile responses could be blocked by selective α2‐adrenoceptor antagonists. The adrenergic contractile response demonstrated this ‘feed‐back’ even on the second pulse at 0.5 Hz. Endogenous inhibition of the ‘non‐adrenergic’ contraction required higher frequencies or enhancement of the extracellular concentration of noradrenaline by blockade of its neuronal uptake.
Contractile responses to exogenous noradrenaline were abolished by nifedipine, at a concentration that did not affect the adrenergic (IIs) neurotransmission.
These results reinforce the view that part of the motor transmission in rat vas deferens is non‐adrenergic and allow the disentanglement of the various postjunctional and prejunctional elements contributing to the complex response to a train of stimuli.
Plasma acid phosphatase levels in endotoxaemia: modification by drugs and chemically detoxified endotoxins
Authors: Godin David V. , Tuchek John M. 
Published: July 2012

The ability of chemically detoxified E. coli endotoxins and membrane‐active agents to modify the toxicity of native E. coli endotoxin in vivo was examined.
The time‐ and dose‐dependent increase in plasma acid phosphatase activity following toxin administration to rats provided a convenient quantitative measure of in vivo toxicity under various experimental conditions.
Treatment of endotoxin with either sodium hydroxide or sodium periodate produced substances which, when injected alone, failed to cause an increase in plasma acid phosphatase activity. When given before native endotoxin, periodate‐detoxified toxin produced a dose‐dependent reduction in the elevation of plasma enzyme activity caused by unmodified toxin. Pretreatment with pranolium, hydrocortisone or (+)‐propranolol also reduced the in vivo toxicity of endotoxin.
Mortality studies in mice provided further independent support for the effectiveness of periodate‐detoxified endotoxin and membrane‐active drugs as endotoxin antagonists.
Evidence has been found that under certain conditions gentamicin may act synergistically with bacterial endotoxins in vivo.
Depolarization of rat isolated superior cervical ganglia mediated by β2‐adrenoceptors
Authors: Brown D.A. , Dunn P.M. 
Published: July 2012

Depolarizations of freshly‐dissected isolated superior cervical ganglia of the rat were recorded extracellularly. The following sympathomimetic amines (in order of decreasing potency) produced depolarizations of up to 0.4 mV: isoprenaline, salbutamol, adrenaline, noradrenaline. Depolarizations were lost after overnight storage, leaving only hyperpolarizing responses.
Depolarizations by isoprenaline were antagonized by (‐)‐propranolol (pA2 8.94 ± 0.15), (±)‐butoxamine (pA2 7.36 ± 0.12) and (±)‐practolol (pA2 5.14 ± 0.13). They were not blocked by phentolamine (1 μm) or phenoxybenzamine (1 μm). Isoprenaline and salbutamol were antagonized with equal facility by practolol or butoxamine.
In concentrations producing ganglionic depolarization, these compounds also produced a smaller depolarization of presynaptic elements in the ganglion, but not preganglionic trunk fibres. Presynapic depolarization was blocked by 100 nM propranolol but not by 1 μm phentolamine.
Isoprenaline and salbutamol increased the amplitude of the compound ganglionic action potential recorded following single preganglionic nerve stimuli when transmission had been rendered submaximal by adjusting the Ca/Mg ratio, but not in normal solution.
Isoprenaline (0.1 μm) also increased the amount of [3H]‐acetylcholine released by preganglionic stimulation in low Ca/high Mg solution.
It is concluded that facilitatory adrenoceptors are present on pre‐ and postsynaptic elements in rat superior cervical ganglia, which resembles the ‘β2’ subclass of β‐receptors.
The effect of choline mustard on the rat superior cervical ganglia
Authors: Allen M.C. 
Published: July 2012

The effect of choline mustard aziridinium ion (ChM) on the isolated superior cervical ganglion of the rat was investigated.
In the presence of ChM (22.5 μM), stimulation at 1 Hz resulted in a slowly developing blockade of transmission, which did not occur at a stimulus frequency of 0.1 Hz.
Choline (0.1 mm) slowed the onset of the blockade produced by stimulation at 1 Hz in the presence of ChM.
The presence of excess thiosulphate ions prevented the action of ChM on the transmission in the superior cervical ganglion.
Treatment of the ganglion with ChM (22.5 μm) only slightly inhibited the depolarization produced by carbachol (dose ratio 1.3), suggesting the drug produced a small degree of receptor blockade.
[3H]‐choline accumulation in the rat superior cervical ganglia displays several components: (a) sodium‐dependent high affinity uptake (SDHAU) that can be activated further by preincubation in a high concentration of K+ ions; (b) sodium‐dependent low affinity uptake (SILAU); (c) linear diffusional accumulation which does not saturate.
Hemicholinium‐3 selectively inhibits the activated sodium‐dependent high affinity uptake, but is a weak inhibitor of resting sodium‐dependent high affinity uptake and sodium‐independent low affinity uptake.
ChM inhibits both activated and resting sodium‐dependent high affinity uptake, but is a very weak inhibitor of sodium‐independent low affinity uptake. Homocholine shows similar selectivity.
ChM inhibition of activated sodium‐dependent high affinity uptake is very much more persistent than that of hemicholinium‐3.
Hemicholinium‐3 and ChM both inhibit [3H]‐acetylcholine synthesis.
Age‐dependent differences in the positive inotropic effect of phenylephrine on rat isolated atria
Authors: Hashimoto Hisakuni , Nakashima Mitsuyoshi , Sugino Naoko 
Published: July 2012

The age‐dependent differences in the involvement of α‐adrenoceptors in the positive inotropic effect of phenylephrine (Phe) were examined in isolated atria of male Wistar rats 6 weeks (6W), 10 weeks and 7 months (7M) of age.
The maximal increase in tension development induced by Phe increased with age, whereas the EC50 values for the positive inotropic effect of Phe did not change with age. The inhibitory effect of phentolamine on the response to Phe increased with age. Propranolol caused only slight inhibition of the effect of Phe in both 6W and 7M rats, and the EC50 values for Phe in the presence of propranolol did not change significantly with age.
The EC50 values for isoprenaline and 5‐hydroxytryptamine in 7M rats were higher than those in 6 W rats.
In 7M rats, the duration of the tension development was only slightly affected by Phe in the presence or absence of propranolol, but it was markedly decreased by Phe in the presence of phentolamine.
The dose‐response curve for Phe was markedly shifted to the left by papaverine in 6W rats, but slightly in 7M rats. The dose‐response curve for isoprenaline was markedly shifted to the left by papaverine in both groups.
These results are consistent with effects of Phe being mediated by both α‐ and β‐adrenoceptors in both 6W and 7M rats, but there is a shift in the balance from rather more β‐receptors in the young animals to more α‐receptors in the adults.