bluuebunny/crossref_metadata_2025_split huggingface dataset:
INTRARENAL STIMULATION OF RENIN SECRETION BY FRUSEMIDE IN THE ISOLATED KIDNEY OF THE RAT
Authors: VANDONGEN R. 
Published: July 2012

Intrarenal infusion of frusemide markedly stimulated renin secretion in the isolated perfused kidney of the rat.
Renin values increased from 24 ± 6 to 195 ± 34 units of secretion rate (renin concentration (nmol angiotensin I/h per litre) × flow rate (ml/min)) following administration of frusemide for 8 min, compared with corresponding control values of 13 ±2 (P >0.05) and 47 ±18 (P < 0.001). This stimulatory effect was also observed when urine flow was interrupted by ligation of the ureters.
The changes in renal perfusion pressure and perfusate flow rate were not significantly different from the control values.
These findings indicate the existence of an intrarenal site of action for frusemide on renin secretion.
Since frusemide did not appear to alter perfusion pressure or flow rate, and was effective when urine flow was abolished, a dominant role for a vascular or macula densa receptor mechanism seems unlikely. A direct effect of frusemide on the renin secreting cell is therefore suggested.
SELECTIVITY OF BLOCKING AGENTS FOR PRE‐ AND POSTSYNAPTIC α‐ADRENOCEPTORS
Authors: DOXEY J.C. , SMITH C.F.C. , WALKER JULIE M. 
Published: July 2012

Low frequency (0.1 Hz) electrical stimulation of the rat isolated vas deferens produced regular contractions that were inhibited by low concentrations of clonidine.
The inhibition of the vas deferens produced by clonidine was presynaptic in origin and involved α‐adrenoceptors.
Presynaptic α‐adrenoceptor antagonist activity was assessed by studying the effects of increasing concentrations of the antagonists on cumulative clonidine dose‐response curves on the stimulated vas deferens.
Postsynaptic α‐adrenoceptor antagonist activity was assessed by comparison of control cumulative noradrenaline dose‐response curves with those in the presence of increasing concentrations of antagonists in the rat anococcygeus muscle.
The results indicate that yohimbine and phentolamine are more potent in blocking presynaptic than postsynaptic α‐adrenoceptors. Phenoxybenzamine and prazosin block postsynaptic α‐adrenoceptors preferentially.
The findings support the view that presynaptic and postsynaptic α‐adrenoceptors differ in their sensitivity to α‐adrenoceptor antagonists.
RESPONSES OF THE CARDIOVASCULAR SYSTEM OF THE RAT TO NORADRENALINE INFUSIONS AND THEIR MODIFICATION BY ADRENOCEPTOR BLOCKING AGENTS
Authors: IMMS F.J. , NEAME R.L.B. , POWIS D.A. 
Published: July 2012

The effects of noradrenaline upon the cardiovascular system of the rat, anaesthetized with pentobarbitone, have been investigated.
Noradrenaline produces a dose‐dependent increase in mean arterial blood pressure (MABP) which is due entirely to an increase in cardiac output; total peripheral vascular resistance (TPR) remains unchanged.
Following β‐adrenoceptor blockade the pressor response to infused noradrenaline is enhanced and is now due mainly to an increase in TPR; the increment in cardiac output is reduced.
After α‐adrenoceptor blockade the pressor response is greatly reduced; the residual increase in MABP is due solely to an increase in cardiac output.
After ganglion blockade resting cardiac output and TPR both fall, resulting in a reduction in MABP. The pressor response to noradrenaline is enhanced and is now due to increases in both TPR and in cardiac output.
The cardiovascular response of the anaesthetized rat to noradrenaline can be explained in terms of classical α‐ and β‐adrenoceptor stimulation by the amine; the unusual form of the response may be due to an effective predominance of β‐adrenoceptor‐mediated effects in this species.
It is suggested that the failure of exogenous noradrenaline to produce a rise in TPR results from a balance between the α‐adrenoceptor‐mediated increase and β‐adrenoceptor‐mediated decrease in this variable. However, this proposed balance is lost if resting vasoconstrictor tone is reduced by ganglion blockade.
STRUCTURE‐ACTIVITY RELATIONSHIPS FOR THE ANTICHOLINOCEPTOR ACTION OF TRICYCLIC ANTIDEPRESSANTS
Authors: SHEIN KIN , SMITH S.E. 
Published: July 2012

The anticholinoceptor action of 15 tricyclic antidepressants and derivatives has been studied on the guinea‐pig ileum. At the muscarinic receptors the compounds were found to exert antagonism which was reversible and apparently competitive up to dose‐ratios of around 100 but non‐competitive above this level.
Log affinity constants were derived from log dose‐response curves at dose‐ratios <100, where parallel curves were obtained. Amitriptyline, the most potent compound, had 214 × the potency of the weakest, hydroxyimipramine, but was itself 20 × weaker than atropine.
Structure‐activity studies showed that dibenzocycloheptane derivatives were more potent than dibenzazepines and that S or O substitution for C‐11 or other major changes in the central ring of the tricyclic nucleus greatly reduced activity. Side‐chain N‐methylation increased potency markedly. This and other findings indicate that both tricyclic nucleus and side‐chain receptor attachments are largely non‐polar in type.
TOLMESOXIDE, A DRUG THAT LOWERS BLOOD PRESSURE BY A DIRECT RELAXANT EFFECT ON VASCULAR SMOOTH MUSCLE
Authors: DOXEY J.C. 
Published: July 2012

The blood pressure of conscious normotensive, deoxycorticosterone acetate (DOCA) hypertensive and 1 kidney Goldblatt hypertensive rats and renal hypertensive and normotensive cats was reduced by tolmesoxide (4,5‐dimethoxy‐o‐tolyl methyl sulphoxide).
Tachycardia accompanied the hypotension. In rats the increase in heart rate was abolished by concurrent administration of propranolol. Tachycardia did not occur in pithed rats.
Vasoconstriction induced by sympathetic stimulation, noradrenaline, tyramine, angiotensin or vasopressin was antagonized by tolmesoxide.
The antagonism of vasoconstrictor responses produced by tolmesoxide was unaffected by β‐adrenoceptor, muscarinic or histamine antagonists.
It is concluded that the lowering of pressure produced by tolmesoxide results from a direct relaxant effect on vascular smooth muscle.
REGIONAL BRAIN ATROPHY AND REDUCTIONS IN GLUTAMATE RELEASE AND UPTAKE AFTER INTRASTRIATAL KAINIC ACID
Authors: FRIEDLE N.M. , KELLY P.H. , MOORE K.E. 
Published: July 2012

Neurochemical changes and tissue weights were measured following intrastriatal injection of 2.5 μg of kainic acid in 2 μl of 0.9% w/v NaCl solution (saline) in the rat.
After kainic acid the striatum and neocortex on the injected side showed a progressive reduction in weight, the neocortex showing the greatest absolute weight loss and the striatum the greatest percentage change.
Large (80–90%) reductions in choline acetyltransferase (CAT) and l‐glutamate decarboxylase (GAD) activities in the striatum occurred within 2–4 days of the injection and persisted at least 10 weeks. At 10 weeks CAT and GAD activities were unaltered in the neocortex.
The absolute content of dopamine in the striatum was not different from control 5 days after the injection of kainic acid but was reduced at 2 and 10 weeks. At 2 weeks the concentration (μg/g wet weight) of dopamine also was reduced but at 10 weeks it was near normal due to atrophy of the striatum.
The high affinity glutamate uptake into a crude synaptosomal preparation of the striatum was reduced by 64% 5 days after kainic acid and was still reduced by 67% at 10 weeks.
The efflux of glutamate from slices of the striatum in the presence of 52 mm K+ was reduced by approximately 75% 5 days and 15 weeks after kainic acid.
In vitro kainic acid (10−4m) neither altered the high affinity uptake of radiolabelled glutamate into a homogenate of the striatum, nor released endogenous glutamate from slices of striatum.
INVOLVEMENT OF THE PERIAQUEDUCTAL GREY MATTER AND SPINAL 5‐HYDROXYTRYPTAMINERGIC PATHWAYS IN MORPHINE ANALGESIA: EFFECTS OF LESIONS AND 5‐HYDROXYTRYPTAMINE DEPLETION
Authors: DEAKIN J.F.W. , DOSTROVSKY J.O. 
Published: July 2012

Electrolytic lesions of the periaqueductal grey matter (PAG) were made in rats. The analgesia produced by intraperitoneal injection of morphine (10 and 20mg/kg), tested by the tail flick and hot plate methods, was substantially reduced in the lesioned rats. Baseline pain thresholds were unaffected by the lesions.
The lesion effects were not due to damage to the dorsal raphe nucleus. The extent of histologically determined damage to the dorsal raphe and the resulting decrease in striatal 5‐hydroxytryptamine (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA) concentrations did not correlate with the reduction in morphine analgesia produced by the lesion. Furthermore, microinjections of 5, 6‐diHYDROXYTRYPTAMINE (5,6‐DHT) into the dorsal raphe nucleus produced a similar fall in 5‐HIAA levels but had no effect on morphine analgesia.
Selective destruction of the periventricular catecholamine system produced by microinjection of 6‐hydroxydopamine (6‐OHDA) caused a slight decrease in morphine analgesia, thus raising the possibility that catecholamines may be involved in the action of morphine in the PAG.
5,7‐Dihydroxytryptamine‐induced lesions of the spinal cord 5‐hydroxytryptaminergic pathways reduced cord 5‐HT concentration by 70% and markedly attenuated morphine analgesia as determined by the tail flick test.
These experiments provide additional evidence that the PAG is a major site of action of opiates in producing analgesia. Furthermore, they have demonstrated the probable involvement of spinal 5‐hydroxytryptaminergic pathways in the mediation of opiate analgesic effects.
INTERACTION OF PENTOBARBITONE AND γ‐AMINOBUTYRIC ACID ON MAMMALIAN SYMPATHETIC GANGLION CELLS
Authors: BROWN D.A. , CONSTANTI A. 
Published: July 2012

Interactions of bath‐applied pentobarbitone and γ‐aminobutyric acid (GABA) on neurones in isolated superior cervical ganglia of the rat have been examined with intracellular microelectrodes.
Pentobarbitone itself (30 μm‐1 mm) showed no clear or consistent GABA‐like effects: changes in resting input conductance and membrane potential were small and variable.
Pentobarbitone (100 μm) strikingly enhanced the conductance increases produced by GABA and 3‐aminopropanesulphonic acid, and reversed the depression of GABA‐evoked responses by bicucul‐line.
It is concluded that reversal of bicuculline action at the membrane conductance level might be explained by augmentation of GABA‐action. This augmentation cannot be attributed to ‘partial agonist’ properties of pentobarbitone or to interference with glial transport processes.
INHIBITION OF PRECURSOR INCORPORATION INTO NUCLEIC ACIDS OF MAMMALIAN TISSUES BY ANTIMALARIAL AMINOQUINOLINES
Authors: FIELD ROGER C. , GIBSON BETSY R. , HOLBROOK DAVID J. , MCCALL BARBARA M. 
Published: July 2012

Chloroquine, primaquine and ethidium inhibited thymidine incorporation into deoxyribonucleic acid of rat tissues when administered concurrently with the labelled precursor.
Chloroquine and primaquine inhibited the incorporation of uridine and adenine, but not orotate, into various ribonucleic acid fractions of liver of rats and mice. These drugs had no effect on leucine incorporation into hepatic protein in rats or mice.
Although chloroquine and primaquine are active against different stages in the life cycle of the malarial parasites, the two aminoquinolines exert similar effects in rodent tissues.
AN in vitro COMPARISON OF β‐ADRENOCEPTOR STIMULANTS ON POTASSIUM‐DEPOLARIZED UTERINE PREPARATIONS FROM GUINEA‐PIGS
Authors: O'DONNELL STELLA R. , PERSSON C.G.A. , WANSTALL JANET C. 
Published: July 2012

A comparison of six β‐adrenoceptor stimulants has been carried out on in vitro preparations of guinea‐pig uterus which were depolarized in K+‐Krebs solution. Results have also been obtained on uterine preparations in which contractions to acetylcholine were inhibited. The establishment of the conditions for the K+‐depolarized preparations are described.
There was no significant difference between potency values (mean neg log EC50 values) for any of the drugs on the two types of uterine preparation i.e. the preparations had the same sensitivity to the drugs.
There was a less than two‐fold difference between the relative potency values for the β‐adrenoceptor stimulants on the two types of uterine preparation. The relative potency values (isoprenaline = 100) on the K+‐depolarized preparation were fenoterol 74.1, salbutamol 15.1, rimiterol 13.5, terbutaline 8.2 and orciprenaline 5.6.
The relative potency values obtained on uterine preparations were less than three‐fold different from those previously found for guinea‐pig trachea (after inhibition of extraneuronal uptake).
The pA2 value for propranolol on the K+‐depolarized uterine preparations was 9.13.
It is concluded that the K+‐depolarized guinea‐pig uterine preparation can be used for quantitative studies on β‐adrenoceptor stimulant drugs. It lacks spontaneous activity, drugs can be added cumulatively and several drugs can be compared on a single preparation. In addition, the results obtained support the classification of the β‐adrenoceptors in guinea‐pig uterus and trachea in the same sub‐group (β2).
THE ANTIPYRETIC EFFECT OF TILORONE HYDROCHLORIDE IN THE CAT
Authors: CLARK WESLEY G. , ROBINS JEAN A. 
Published: July 2012

The antipyretic activity of tilorone hydrochloride was studied in conscious, unrestrained cats provided with implanted jugular venous catheters, third cerebral ventricular (i.c.v.) cannulae and retroperitoneal thermocouples.
In afebrile animals, 10 mg/kg i.v. or 1 mg i.c.v. tilorone hydrochloride did not alter body temperature, but 20 mg/kg i.v. or 2 to 5 mg i.c.v. caused hypothermia and various behavioural responses.
Non‐hypothermogenic doses of tilorone (i.v. or i.c.v.) antagonized hyperthermic responses to leucocytic pyrogen (i.v. or i.c.v.), bacterial pyrogen (i.c.v.) and sodium arachidonate (i.c.v.) but did not antagonize prostaglandin E1 (i.c.v.).
These results indicate that tilorone has an antipyretic action within the central nervous system that is distinct from its hypothermogenic action. Although there is no published evidence to indicate that tilorone can inhibit prostaglandin synthesis peripherally, its ability to reduce hyperthermic responses to arachidonate suggests that it can inhibit prostaglandin synthesis within the brain.
COMPARISON OF THE EFFECTS OF ULTRAVIOLET LIGHT AND PURINERGIC NERVE STIMULATION ON THE GUINEA‐PIG TAENIA COLI
Authors: BURNSTOCK G. , WONG H. 
Published: July 2012

The responses of the guinea‐pig taenia coli, urinary bladder and the rabbit portal vein to ultraviolet (u.v.) light were compared to those elicited by purinergic nerve stimulation and exogenous adenosine triphosphate (ATP).
In the presence of sodium nitrite, u.v. light between 340‐380 nm produced a maximum relaxation of the taenia coli. The relaxation was reversible and fast in onset. It was unaffected by atropine, guanethidine or low concentrations of phentolamine or propranolol. When the tone was low, the relaxation was usually followed by a ‘rebound contraction’ upon cessation of stimulation. Thus, the response to u.v. light closely resembles the responses to both purinergic nerve stimulation and exogenously applied ATP.
U.v. light did not initiate impulses in purinergic nerves since its action was unaffected by tetrodotoxin; nor did it release ATP from nerve terminals (in contrast to its release during purinergic nerve stimulation). The adenosine‐uptake inhibitor, dipyridamole, which potentiates the responses to purinergic nerve stimulation and ATP, did not affect the response to u.v. light.
Agents known to alter postjunctional responses to purinergic nerve stimulation and ATP also altered the response to u.v. light. High concentrations of the 2‐substituted imidazoline compounds, antazoline and phentolamine, which antagonize the responses to purinergic nerve stimulation and ATP, reduced the responses to u.v. irradiation. The prostaglandin synthesis inhibitor, indomethacin, which abolishes the ‘rebound contraction’ following stimulation of purinergic nerves, also blocks the ‘rebound ‘contraction’ following u.v. irradiation. Increases in the K+ concentration produced parallel changes in the inhibitory responses to u.v. light and purinergic nerve stimulation.
U.v. light produced relaxation and inhibition of spontaneous activity of the rabbit portal vein (relaxed by ATP), but had no effect on the guinea‐pig urinary bladder (contracted by ATP) and ureter (unaffected by ATP).
It is suggested that u.v. light is acting on some part of the purinergic receptor complex which is involved in the mediation of inhibitory responses to ATP and purinergic nerve stimulation, and may therefore provide a way of investigating the chemistry of inhibitory purinergic receptors.
THE EFFECTS OF A TOXIN ISOLATED FROM AUSTRALIAN TIGER SNAKE (Notechis scutatus scutatus) VENOM ON AUTONOMIC NEŮOMUSCULAR TRANSMISSION
Authors: HARRIS J.B. , ZAR M.A. 
Published: July 2012

The effects on mammalian autonomic neuromuscular transmission of a purified toxin from the crude venom of the Australian tiger snake, Notechis scutatus scutatus, have been investigated.
The toxin had no measurable effect on transmission in either the rat anococcygeus, the rat vas deferens, or the longitudinal muscle of the guinea‐pig ileum.
The toxin induced a contraction of longitudinal smooth muscle of the ileum. The tissue relaxed in spite of the continued presence of the toxin, and remained insensitive to further doses. The contractile response was not mediated by either cholinergic or histaminergic mechanisms.
The toxin caused an inhibition of the response to field stimulation of the guinea‐pig vas deferens and the guinea‐pig seminal vesicle. The inhibition was spontaneously reversible, and the preparations remained insensitive to further doses of the toxin. The effects of the toxin were not mediated by either prostaglandins or by noradrenaline.
The inhibitory effects of a variety of compounds known to act at presynaptic sites were also blocked by exposure to the toxin; inhibition caused by postsynaptic activity was unaffected by the toxin.
It is suggested that the toxin inhibits transmission in the guinea‐pig vas deferens and seminal vesicle by a presynaptic mechanism.
The possibility that the mechanism involves phospholipase A2 activity is discussed.
THE DEVELOPMENT OF TOLERANCE TO KETAMINE IN RATS AND THE SIGNIFICANCE OF HEPATIC METABOLISM
Authors: LIVINGSTON A. , WATERMAN A.E. 
Published: July 2012

A decrease in sleeping time in rats pretreated with ten daily doses of ketamine compared to controls is shown.
This decrease in sleeping time is associated with a more rapid decrease in circulating and brain levels of ketamine and its N‐demethylated metabolite and higher levels of the subsequent oxidation metabolite in the pretreated animals.
Metabolism of ketamine to its N‐demethylated metabolite by liver homogenates in vitro was more rapid when the livers were obtained from ketamine pretreated rats.
Microsomal preparations from rat liver were capable of metabolizing ketamine to its N‐demethylated metabolite and this metabolite to the subsequent oxidation metabolite in vitro. The Vmax and Km for the first reaction calculated from loss of substrate were 433 mol mg−1 protein h−1 and 0.133 mm respectively and 199 nmol mg−1 protein h−1 and 0.121 mm for the second reaction.
The results indicate that tolerance to ketamine in rats is associated with increased hepatic metabolism which can also be demonstrated in vitro in liver homogenates.
STIMULATION OF ACETYLCHOLINE OUTPUT FROM BRAIN SLICES CAUSED BY THE IONOPHORES BrX‐537A AND A 23187
Authors: CASAMENTI F. , MANTOVANI P. , PEPEU G. 
Published: July 2012

The effect of two ionophores, BrX‐537A (Bromolasolacid) and A 23187, on acetylcholine (ACh) output from brain slices was studied.
The slices were prepared from rat cerebral cortex, incubated in Krebs solution containing physo‐stigmine and ACh output determined by bioassay.
Both ionophores enhanced ACh output. BrX‐537A exerted its maximal effect, a six fold increase, at a concentration of 1.8 μm, while A 23187 caused a three fold increase at a concentration of 58 um.
When the slices were incubated in a Ca‐free medium, the effect of A 23187 on ACh output was abolished while that of BrX‐537A was only reduced. BrX‐537A was also active when disodium edetate (EDTA) was added to the Ca‐free medium.
The activity of BrX‐537A was not affected by the presence of tetrodotoxin in the incubation medium.
The stimulation of ACh output elicited by KC1 (25 him) was increased further by hyoscine, but not by BrX‐537A. Hyoscine however had no effect when ACh output was stimulated by BrX‐537A.
The effect of BrX‐537A on ACh output was potentiated by the addition of Mg2+ (9.3 mm) to the incubation medium and was reduced in a Mg‐free medium.
It is concluded that A 23187 stimulates ACh output by transporting extracellular Ca2+ into cholinergic nerve endings. The effect of BrX‐537A does not depend only on Ca2+ but also on other mechanisms.
ANTAGONISM OF THE EFFECTS ON THERMOREGULATION OF Δ9‐TETRAHYDROCANNABINOL BY CLOMIPRAMINE IN THE RAT
Authors: FENNESSY M.R. , TAYLOR D.A. 
Published: July 2012

The effect of pretreatment with clomipramine hydrochloride (15 mg/kg, i.p.) on the (‐)‐trans‐A9‐tetrahydrocannabinol (A9‐THC)‐induced changes in body temperature and brain amines of the rat was investigated.
A dose of 0.05 mg/kg of A9‐THC produced hyperthermia and a decrease in whole brain concentration of 5‐hydroxyindoleacetic acid (5‐HIAA). Doses of 2 and 5 mg/kg produced hypothermia and increases in brain 5‐HIAA whereas 0.5 mg/kg did not affect either parameter. A9‐THC, at any of the doses, did not affect the whole brain concentrations of dopamine, noradrenaline or 5‐hydroxytryptamine.
Clomipramine modified these responses of A9‐THC in that the dose‐response curves appeared to be shifted to the right.
It is concluded that clomipramine acts as an antagonist to these actions of A9‐THC by interfering with entry of A9‐THC into tryptaminergic neurones.
THE EFFECTS OF METHOTREXATE AND MELPHALAN IN SHEEP
Authors: GREENWOOD B. , KERRY P.J. 
Published: July 2012

Sheep were injected with either methotrexate or melphalan in an attempt to lower the numbers of neutrophil granulocytes in peripheral blood.
Methotrexate, 5.0 mg/kg intravenously, on three consecutive days, produced no noticeable clinical or haematological changes.
A single dose of melphalan, 1.0 mg/kg intravenously, depleted lymphocytes and granulocytes, but the numbers of the latter then rose to values exceeding the levels before melphalan treatment. Doubling the dose of melphalan proved fatal.
The failure of methotrexate to produce changes can be explained in terms of ruminant metabolism.
ACETYLCHOLINE AND SOMATICALLY EVOKED INHIBITION ON PERIGENICULATE NEURONES IN THE CAT
Authors: GODFRAIND J.M. 
Published: July 2012

Perigenicuiate neurones in cats were found to be inhibited by iontophoretically applied acetylcholine (ACh) and some of them by somatic sensory stimulation under certain experimental conditions.
Under chloralose anaesthesia, perigenicuiate neurones could be divided into two groups with regard to their spontaneous activity, sensitivity to glutamate and reaction to sensory inputs. Somatic sensory stimulation clearly inhibited the glutamate discharges of those perigenicuiate neurones which were characterized by a high sensitivity to glutamate and the absence of spontaneous activity. ACh had no clear inhibitory effect.
Under fluothane and urethane anaesthesia, no somatic sensory influence was noticed but ACh depressed almost all perigenicuiate neurones.
In an unanaesthetized midpontine pretrigeminal preparation, the inhibitory effect of ACh was confirmed.
No conditions were found under which the inhibitory influences of ACh and those of somatic sensory stimulation could be observed simultaneously on the same neurone. Therefore, it could not be established whether ACh mediates the somatic sensory influences on perigenicuiate cells.