bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the specificity and type of receptor involved in carotid body chemoreceptor activation by adenosine in the cat
Authors: McQueen D.S. , Ribeiro J.A. 
Published: July 2012

Experiments were performed on cats anaesthetized with pentobarbitone in which carotid chemoreceptor activity was recorded from the peripheral end of a sectioned carotid sinus nerve.
Intracarotid injections of adenosine 5′‐triphosphate (ATP) (1–100 μg i.e.) caused a dose‐related increase in chemosensory discharge which was delayed in onset.
The adenosine uptake inhibitor dipyridamole potentiated the chemoexcitatory effects of injected adenosine and ATP.
The stable ATP analogue α‐β‐methylene ATP (10–100 μg i.c.) depressed chemoreceptor discharge, which suggests the presence of a P2‐purinoceptor in the carotid body, and provides evidence that the chemoexcitatory effect of ATP results from its hydrolysis to adenosine 5′‐phosphate (AMP)/adenosine.
Adenine, inosine, guanosine, cytidine and uridine had no appreciable effect on chemoreceptor discharge.
The adenosine R‐site agonists 2′‐chloroadenosine and N6‐methyladenosine had chemoexcitatory effects which were similar to those of adenosine, whereas the P‐site agonist 2′‐deoxyadenosine had no appreciable effect on discharge.
We conclude that the adenosine receptor in the cat carotid body has some of the characteristics of an R‐site receptor according to the classification of Londos & Wolff (1977).
Characterization of the binding of dl‐[3H]‐2‐amino‐4‐phosphonobutyrate to l‐glutamate‐sensitive sites on rat brain synaptic membranes
Authors: Butcher S.P. , Collins J.F. , Roberts P.J. 
Published: July 2012

The binding of dl‐[3,4‐3H] 2‐amino‐4‐phosphonobutyric acid dl[3H]‐APB to rat whole brain synaptic membranes was investigated.
Binding was linear with membrane protein concentration, and optimal at physiological pH and temperature. The association rate was rapid, achieving equilibrium within 10 min. Prolonged incubations (> 20 min) revealed additional sites, which apparently possessed identical binding characteristics to those detected with 10 min incubations.
Binding of dl‐[3H]‐APB was enriched in synaptic membrane fractions, and assessment of the regional distribution, indicated greatest binding in those areas with a rich glutamatergic innervation.
The binding of dl‐[3H]‐APB in HEPES‐KOH buffer exhibited an absolute requirement for Cl−. The addition of Ca2+ resulted in a further enhancement of binding.
Saturation analysis revealed the presence of specific glutamate‐sensitive dl‐[3H]‐APB binding sites, with a KD = 1.26 μm and Bmax = 12.08 pmol mg−1 protein. A Hill plot revealed a slope slightly greater than unity, which could possibly be a reflection of a contribution to binding of a further site which is relatively insensitive to glutamate. Analysis of 60 min incubation data indicated an approximately 3 fold increase in the capacity of the system, but a relatively unchanged KD.
Examination of the pharmacological specificity of binding, showed that for both agonist and antagonist molecules, the l‐enantiomers were invariably more active than the d‐forms. For example, the l‐(+)‐2‐amino‐4‐phosphonobutyrate isomer was 15 times more active than the d‐(−)‐form in inhibiting the binding of dl‐[3H]‐APB. This is in close agreement with the ability of these compounds to produce depression of synaptic transmission. The most potent inhibitor of binding was quisqualate. It is suggested that APB may interact with a quisqualate‐preferring class of excitatory amino acid receptors, possibly localised predominantly on presynaptic terminals.
Lanthanides are transported by ionophore A23187 and mimic calcium in the histamine secretion process
Authors: Amellal M. , Landry Y. 
Published: July 2012

Ionophore A23187 induced histamine release from peritoneal rat mast cells in the presence of lanthanum or terbium as it did in the presence of calcium.
Low concentrations of lanthanides (10−5 to 2 × 10−4m) were more efficient than similar concentrations of calcium.
The effect of low concentrations of calcium and lanthanides were additive.
Increasing the concentration of lanthanides above 10−3 m decreased histamine release. This decrease was partly reversed by calcium.
Calmodulin inhibitors, phenothiazines, R24571 and mepacrine, inhibited the histamine release induced by either calcium or lanthanides.
Zn2+, a calmodulin inhibitor transported by A23187, inhibited more potently the calcium‐dependent histamine release.
Lanthanides decrease histamine release induced by 48/80 in the absence of added calcium.
These data show that ionophore A23187 can transport lanthanides across the plasma membrane of mast cells, allowing the trivalent cations to substitute for calcium in the activation of calmodulin or calmoduline‐like proteins.
Differential effect of acetylsalicylic acid and dipyrone on prostaglandin production in human fibroblast cultures
Authors: Lüthy Christa , Multhaupt Marcel , Oetliker Oskar , Perisic Miodrag 
Published: July 2012

Human skin fibroblasts incubated with arachidonic acid in culture show basal release of prostaglandins. They produce the same prostaglandins after stimulation with bradykinin.
Basal release of prostaglandins I2 (6‐oxo‐PGF1α), F2α and E2 is inhibited dose‐dependently by both acetylsalicylic acid (ASA) and dipyrone (P < 0.05). The examined dose‐range was 10−7 to 10−4 M for both drugs. During the first 5 min after removal of the drugs from the incubation medium, bradykinin‐stimulated release remains dose‐dependently inhibited (P < 0.001) in ASA‐, but not in dipyrone‐treated cultures. The difference between the effects of ASA and of dipyrone is highly significant (P < 0.0001), whereas the dipyrone‐treated cultures are not different from controls.
The findings are consistent with cyclo‐oxygenase inhibition by ASA as well as by dipyrone. However, the data demonstrate rapid reversibility of the effect of dipyrone. This suggests that in contrast to ASA, dipyrone does not inhibit cyclo‐oxygenase by binding covalently to the enzyme.
The source of thromboxane and prostaglandins in experimental inflammation
Authors: Higgs G.A. , Moncada S. , Salmon J. A. , Seager Kaye 
Published: July 2012

Although cyclo‐oxygenase products have been detected at inflammatory sites the tissue of origin remains uncertain.
Inflammatory exudates were collected from rats 4, 6, 8, 12 or 24 h after subcutaneous implantation of carrageenin‐impregnated sponges.
Concentrations of the cyclo‐oxygenase products prostaglandin E2 (PGE2), 6‐oxo‐PGF1α and thromboxane B2 (TXB2) in inflammatory exudates and serum (obtained from blood clotted at 37° C) were measured by specific radioimmunoassays.
TXB2 concentrations in exudates increased to about 100 ng ml−1 at 8 h but decreased to less than 20 ng ml−1 after 24 h. PGE2 concentrations increased from 4–12 h and remained between 80 and 120 ng ml−1 from 12–24 h. 6‐oxo‐PGF1α had the same time course as that of PGE2 but concentrations were approximately one third of PGE2 values.
TXB2 concentrations in serum from thrombocytopaenic rats were less than 5% of control values. Thrombocytopaenia did not affect TXB2, PGE2 or 6‐oxo‐PGF1α concentrations or total leukocyte numbers in inflammatory exudates.
Methotrexate‐induced neutropaenia did not affect serum TXB2 concentrations but cyclo‐oxygenase products (including TXB2) in 6 h inflammatory exudates were reduced by 60–95%.
Colchicine (1.0 mg kg−1 s.c.) prevented leukocyte accumulation in sponge exudates and this was accompanied by a reduction in TXB2, PGE2 and 6‐oxo‐PGF1α concentrations at 6 h.
These results indicate that platelets are the source of TXB2 in clotting blood but do not contribute to cyclo‐oxygenase activity in experimental inflammation. The results also suggest that migrating leukocytes are the major source of thromboxane and to a lesser degree prostaglandins in acute 6 h inflammatory exudates.
Effects of LM 5008, a selective inhibitor of 5‐hydroxytryptamine uptake, on blood pressure and responses to sympathomimetic amines
Authors: Ashkenazi R. , Finberg J.P.M. , Youdim M.B.H. 
Published: July 2012

LM 5008 (4‐[2‐(3‐indolyl)ethyl]piperidine) (10, 20 and 50 mg kg−1) had no significant effect on pressor responses to noradrenaline or tyramine in rats anaesthetized with urethane. Desmethylimipramine (1 mg kg−1) blocked the response to tyramine but chlorimipramine (5 mg kg−1) had no significant effect on responses to noradrenaline or tyramine.In the rabbit, anaesthetized with chloralose, LM 5008 (5 mg kg−1) had no effect on pressor responses to noradrenaline, tyramine or angiotensin II, while desmethylimipramine (0.25 mg kg−1) inhibited responses to tyramine and potentiated those to noradrenaline.LM 5008 (10 mg kg−1) had no effect on resting blood pressure of conscious normotensive or DOCA‐saline hypertensive rats.Tranylcypromine (5 mg kg−1) produced a fall in blood pressure in conscious normotensive and in DOCA hypertensive rats.Treatment with a combination of LM 5008 (10 mg kg−1) and tranylcypromine (5 mg kg−1) resulted in the appearance of a behavioural hyperactivity syndrome, but blood pressure was not different from that of animals treated with tranylcypromine alone.These results further demonstrate the selectivity of LM 5008 for 5‐hydroxytryptamine as opposed to catecholamine uptake.
Comparative effects of cotrimoxazole (trimethoprim‐sulphamethoxazole),pyrimethamine‐sulphadiazine and spiramycin during avirulent infection with Toxoplasma gondii (Beverley strain) in mice
Authors: Nguyen B.T. , Stadtsbaeder S. 
Published: July 2012

The antitoxoplasm effects of cotrimoxazole (Ctx), spiramycin (Spir) and pyrimethamine‐sulphadiazine (Pmm‐Sdz) were compared during both proliferative and chronic phases of infection of mice with the Beverley (Bev) strain of Toxoplasma gondii of low virulence.
The therapeutic efficacy of the drugs was determined according to the following criteria: (i) specific antibody response; (ii) acquired resistance to lethal challenge with the virulent RH strain of Toxoplasma; and (iii) persistence of parasites in tissues (brain, liver, spleen) of treated mice.
The results indicated that Ctx, like Pmm‐Sdz, had a greater effect than Spir upon toxoplasma organisms during the proliferative phase of infection. In contrast, none of the three drugs tested was active against tissue cysts in chronically infected mice.
Effects of prostaglandin E2, propranolol and nitroglycerine with halothane, pethidine or pentobarbitone anaesthesia on arrhythmias and other responses to ligation of a coronary artery in rats
Authors: AU T.L.S. , Collins G.A. , Macleod B.A. , Walker M.J.A. 
Published: July 2012

The effects of various cardiovascular drugs (prostaglandin E2 (PGE2), propranolol and nitroglycerine) and anaesthetic regimens (halothane, pethidine and pentobarbitone), upon the outcome of coronary artery ligation in acutely prepared rats were determined.
Effects upon arrhythmias, blood pressure, heart rate, mortality, ECG and the size of the occluded zone were determined for each drug in the presence of each anaesthetic.
PGE2 and nitroglycerine had no statistically significant effects on the outcome of ligation whatever the anaesthetic. Propranolol had limited antiarrhythmic actions.
The anaesthetic used had major effects upon the outcome of ligation, regardless of the cardiovascular drugs administered.
Pentobarbitone anaesthesia resulted in the highest mortality, and most arrhythmias.
Pethidine‐N2O anaesthesia was associated with fewer arrhythmias.
Halothane‐N2O anaesthesia markedly decreased the incidence and severity of arrhythmias, independent of the cardiovascular drug.
It was concluded that the anaesthetic used can have a major influence on ligation‐induced arrhythmias in acutely prepared anaesthetized rats.
Ligand binding to thromboxane receptors on human platelets: correlation with biological activity
Authors: Armstrong Roma A. , Jones R. L. , Wilson N. H. 
Published: July 2012

The preparation of enantiomerically pure [3H]‐15 (S) 9, 11‐epoxymethano PGH2 (a thromboxane A2‐like agonist) has enabled the binding of ligands to the thromboxane receptor of the human platelet to be studied.
The binding of the radio‐ligand to washed human platelets has 3 components. One component is not displaceable by ‘cold’ 9, 11‐epoxymethano PGH2 and its concentration‐binding plot is roughly linear. The other 2 components are displaceable and saturable, and the larger of the two, which is sensitive to the stereochemistry of the C15 secondary alcohol, appears to represent the thromboxane receptor. About 1700 15(S)9, 11‐epoxymethano PGH2 molecules are specifically bound to a single platelet and 50% of this binding is achieved with a concentration of 75 nM.
Displacement of [3H]‐15(S)9, 11‐epoxymethano PGH2 is effected by (a) TXA2 and PGH2 and a number of bicyclic stable analogues (e.g. 9,11‐azo PGH2), all of which produce irreversible aggregation of human platelets; (b) analogues of PGF2α with potent thromboxane‐like activity (e.g. ICI 79939); (c) compounds with partial agonist activity on the platelet thromboxane system (e.g. CTA2); (d) Thromboxane/endoperoxide analogues which specifically antagonize thromboxane‐like actions on the human platelet (e.g. PTA2 and EP 045).
Displacement is not achieved with the natural prostaglandins PGE2, PGD2 and PGF2α. Neither the thromboxane‐synthetase inhibitor dazoxiben nor R(+)‐trimethoquinol have high displacing activity.
The correlation of radio‐ligand displacement with the biological activity of the competing ligands is discussed in relation to the nature of the thromboxane receptor on the human platelet.
Studies in rabbits on the disposition and trypanocidal activity of the antitrypanosomal drug, diminazene aceturate (Berenil)
Authors: Gilbert Robert J. 
Published: July 2012

After intramuscular injection of 3.5 mg kg−1 to rabbits, diminazene aceturate shows biphasic pharmacokinetics with maximum blood and interstitial fluid concentrations occurring after 15 min and 3 h respectively.
Seven days after treatment, 40–50% of the dose had been excreted in the urine and 8–20% in faeces.
Highest diminazene residues were determined in liver: 7 days after dosage, residues of 40.53 ± 4.00 μg−1 were present, corresponding to 35–50% of the dose.
The recommended dose of 3.5 mg kg−1 was not curative for Trypanosoma congolense infections of rabbit but did cause the parasitaemia to become subpatent. A limited prophylactic effect was observed.
Increased 5‐HT2 receptor number in brain as a probable explanation for the enhanced 5‐hydroxytryptamine‐mediated behaviour following repeated electroconvulsive shock administration to rats
Authors: Green A. Richard , Johnson Pauline , Nimgaonkar Vishwajit L. 
Published: July 2012

Following electroconvulsive shock (ECS) administration daily for 10 days there was an increase (35%) in 5‐hydroxytryptamine2 (5‐HT2) receptor number in rat frontal cortex 24 h after the last ECS, compared with handled controls. A similar increase was seen after intermittent ECS administration (5 ECS over 10 days) given during halothane anaesthesia, compared with halothane‐treated controls. The dissociation constant was also increased at this time. A single ECS had no effect.
Treatment of rats with pentylenetetrazol, p‐chlorophenylalanine or α‐methyl p‐tyrosine during the intermittent ECS administration abolished the increase in 5‐HT2 receptor binding.
Since enhanced 5‐HT‐mediated behavioural responses are seen after repeated ECS but not when the ECS is given with the drug treatments outlined above, it is suggested that ECS‐induced enhancement of 5‐HT‐mediated behaviour results from an increase in 5‐HT2 receptor number.
The effects of the antibiotic, primycin, on spontaneous transmitter release at the neuromuscular junction
Authors: Henderson F. , Marshall I.G. 
Published: July 2012

The effects of primycin, a potent ionophore in biological membranes, have been studied at the neuromuscular junction of the garter snake.
Primycin in concentrations greater than 2 × 10−7m produced a time‐ and concentration‐dependent depolarization of twitch muscle fibres.
Primycin (10−7‐5 × 10−7m) produced an increased rate of quantal release of acetylcholine, which was not maintained, and a slight reduction in quantal size. Time to onset and to peak effect of primycin were concentration‐dependent whereas maximum frequency was not.
Absence of extracellular Ca2+ produced a significant delay in the time to onset and to peak effect of primycin, but did not affect the peak miniature endplate potential (m.e.p.p.) frequency.
Following 60 min exposure to primycin (5 × 10−7m), introduction of a high concentration of potassium (20 mm) produced no further increase in spontaneous release.
In cut muscle preparations, exposure to primycin (10−7‐5 × 10−7m) reduced peak endplate current (e.p.c.) amplitude until nerve stimulation resulted in failures or the release of one or two quanta. E.p.c. amplitude was not restored with prolonged washing.
The effects of primycin on the nerve terminal are considered to be consistent with its ability to increase the permeability of membranes to calcium ions resulting in an influx of extracellular calcium, an efflux of mitochondrial calcium and eventual depletion of synaptic vesicles.
Naloxone reduces diuretic responses induced by water, alcohol or congenital lack of vasopressin in rats
Authors: Guiol Chantai , Montastruc Jean‐Louis , Montastruc Paul 
Published: July 2012

The effects of naloxone (2 and 10 mg kg−1 s.c.) were compared in several kinds of experimental polyuria: alcohol‐ or water‐loaded rats and Brattleboro rats (i.e. animals with congenital lack of vasopressin).
In normal rats, both water and alcohol increased urine flow and decreased urinary osmolality. Alcohol induced a more marked diuretic response than water.
In normally hydrated rats, naloxone (2 and 10 mg kg−1 s.c.) failed to modify urine flow, urinary osmolality, Ma+ and K+ urinary excretion, and urine creatinine concentration.
The two doses of naloxone decreased urine flow and increased osmolality in both water‐ and alcohol‐loaded rats.
In Brattleboro rats, naloxone (10 mg kg−1 s.c.) reduced urine flow and urinary creatine whereas the low dose (2 mg kg−1 s.c.) was without effect.
Since it is well known that the mechanism of water‐ or alcohol‐induced diuresis is an inhibition of vasopressin release, the present results suggest that naloxone could prevent this inhibition. They indicate that endogenous opioid peptides may exert an inhibitory control on vasopressin release.
Effects of clonidine and xylazine on body temperature in the rat
Authors: Livingston A. , Low J. , Morris B. 
Published: July 2012

Clonidine and xylazine injected intraperitoneally both produced a dose‐dependent hypothermia in unanaesthetized, freely moving rats.
The α2‐antagonist yohimbine produced an antagonism of the xylazine‐induced hypothermia but a potentiation of the clonidine‐induced hypothermia.
The opioid antagonist naloxone had little effect on the xylazine hypothermia, but potentiated the clonidine hypothermia.
It is concluded that whilst the two α2‐agonists produce a similar hypothermic effect in the rat, they are acting by different mechanisms.
Thiopentone‐induced changes in the contraction pattern of vascular smooth muscle: the influence of albumin
Authors: Andreasen Frederik , Christensen Jørgen H. 
Published: July 2012

The influence of thiopentone on (a) resting tension, (b) contractions evoked by exogenous noradrenaline (NA) and (c) contractions elicited by electrical field stimulation of rings of rabbit pulmonary artery was studied over a concentration range limited by the solubility of the drug.
At thiopentone concentrations from 3 × 10−5 to 1.4 × 10 −3 m in a protein‐free electrolyte solution (K‐H solution) a gradual increase in resting tension to 232% of the control value was observed. The concentration‐effect curve was displaced to the left in the presence of albumin (45 gl−1) at drug concentrations below 1.6 × 10 −4m. Above that concentration the curve was displaced to the right.
The maximal contractile response to exogenous NA in K‐H was reduced from 4.1 to 1.8 g by 5.6 × 10−4m thiopentone, but the effects of low concentrations of NA were potentiated by thiopentone. The concentration‐effect curve for exogenous NA was displaced to the right by albumin itself.
The contractions evoked by electrical field stimulation in K‐H solution were increased by thiopentone up to 2.4 × 10−4m where a maximum of 141 % of the control value was reached. Above that a gradual decrease was observed, the height of the contractions being reduced by 75% of the control value at 1.4 × 10−3m thiopentone. Thiopentone failed to potentiate electrically‐induced contractions in the presence of albumin K‐H, and the concentration‐effect curve for the inhibitory effect of thiopentone was displaced to the right.
From relationships between observed responses and free and total drug concentrations, a procedure was suggested to determine a biologically relevant expression for the thiopentone binding to albumin. The biologically determined albumin binding was always less than the binding determined by equilibrium dialysis, indicating that the fraction of thiopentone bound to albumin could not necessarily be considered biologically inactive.
Structure‐activity studies of homologues of short chain neurotoxins from Elapid snake venoms
Authors: Harvey A.L. , Hider R.C. , Hodges S.J. , Joubert F.J. 
Published: July 2012

Three neurotoxin homologues (CM10 and CM12 from Naja haje annulifera and S5C10 from Dendroaspis jamesoni kaimosae) and two short neurotoxins (CM14 from Naja haje annulifera and erabutoxin b from Laticauda semifasciata)were examined by circular dichroism (c.d.) and tested for neuromuscular activity on chick biventer cervicis nerve‐muscle preparations.
All three homologues had acetylcholine receptor blocking activity, as they abolished responses to indirect stimulation, acetylcholine and carbachol but had no effect on responses to direct muscle stimulation. CM10 was only about 5 times less potent than the short neurotoxin CM14; S5C10 and CM12 were respectively 30 and 300 times less active. The block induced by the three homologues, but not by the neurotoxins, was readily reversed by washing.
CM10 and CM12 had virtually identical cd. spectra which were closely similar to those of the neurotoxins. The spectrum of S5C10 indicated changes in the environment of tyrosine‐25 and in the position of tryptophan‐29. These alterations could distort the 3‐dimensional arrangement of the residues postulated to form the receptor binding site.
The results with CM 10 and CM 12 highlight a role for the first loop (residues 6–16) in the binding of neurotoxins to acetylcholine receptors, in addition to the previously postulated reactive site.