bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissociation of the behavioural and endocrine effects of lysine vasopressin by tryptic digestion
Authors: De WIED D. , GREVEN H. M. , LANDE S. , WITTER A. 
Published: July 2012

Summary
. Lysine vasopressin induces resistance to extinction of active avoidance behaviour (De Wied, 1971).
. Digestion of lysine vasopressin with trypsin almost completely destroys the pressor‐, antidiuretic‐, oxytocic‐ and corticotrophin‐releasing factor activities of lysine vasopressin, but does not materially influence its effect on the maintenance of an avoidance response.
Characterization of angiotensin receptors in vascular and intestinal smooth muscles
Authors: PARK W. K. , REGOLI D. , RIOUX F. 
Published: July 2012

Summary
. A series of analogues of angiotensin II (ATII) has been used in the present experiments to characterize receptors for ATII in intestinal (rat stomach strip, rat colon) and vascular (rabbit aorta) smooth muscles. Two types of compounds have been chosen: (a) agonists with reduced potency, in which 4‐Tyr, 6‐His or 7‐Pro had been substituted with l‐Ala or with Gly and 1‐aminocyclopentane carboxylic acid (Acpc) and (b) competitive antagonists (8‐Gly‐ATII, 8‐Leu‐ATII).
. Replacement of 4‐Tyr, 6‐His and 7‐Pro with l‐Ala decreases the potency, but does not influence the maximum effect of the analogue, while substitution of the same residue with Gly and Acpc reduces both potency and maximum effect.
. Compounds showing full size maximum responses were chosen to establish the following order of potency on the three preparations: ATII>4‐Phe‐ATII> 7‐Ala‐ATII>6‐Ala‐ATII>4‐Ala‐ATII.
. The four derivatives of ATII were completely inactive on tissues desensitized with ATII. The responses to 5‐hydroxytryptamine, acetylcholine and noradrenaline were not significantly modified, except for the rat colon.
. pA2 values for the two competitive antagonists against ATII and 4‐Phe‐ATII were estimated in the three preparations by the use of the cascade superfusion technique. For comparison, pA2 values were also estimated in rat stomach strips and rabbit aortas suspended in a normal organ bath, according to the method of Schild (1947). The similarities of the pA2 values obtained in two series of experiments indicate that (a) the cascade superfusion technique is suitable for this type of study and (b) the receptor for ATII in the three tissues may be the same.
. It is suggested that receptors for ATII in intestinal and vascular smooth muscles may be the same, because (a) the order of potency of various agonists follows the same pattern, (b) the agonists are inactive on tissues desensitized with ATII, (c) pA2 values for competitive antagonists are similar in the three preparations.
On the mechanism of l‐DOPA‐induced postural hypotension in the cat
Authors: DHASMANA K. M. , SPILKER B. A. 
Published: July 2012

Summary
The effects of l‐DOPA on postural hypotension and carotid occlusion pressor effect were studied, mainly in cats the recovery of the blood pressure upon tilting was used as a measure of postural hypotension.
l‐DOPA (30 mg/kg) partially depressed the carotid occlusion pressor effect and caused some degree of postural hypotension, l‐DOPA (100 mg/kg) had more marked effects the responses returned to control after 90 to 150 minutes. l‐DOPA itself caused a pressor response in all cats.
The dopa decarboxylase inhibitor N1‐(dl‐seryl)‐N2‐(2,3,4‐trihydroxybenzyl) hydrazine (RO4‐4602, 50 and 10 mg/kg) had no effect itself on the tilt response but completely prevented the effects of l‐DOPA on the carotid occlusion pressor effect and postural hypotension.
After RO4‐4602 (3 and 1 mg/kg), l‐DOPA (100 mg/kg) caused a brief rise of blood pressure followed by a longer lasting fall in horizontally‐orientated cats (i.e. ‘supine’ hypotension). No postural hypotension was observed after l‐DOPA under these conditions.
Noradrenaline elicited only small and transient effects on postural hypotension, but dopamine's effects were more marked and longer lasting. Pressor dose‐response relationships for noradrenaline were the same before and after l‐DOPA, as well as in cats pretreated with l‐DOPA for 4 days.
In cats with kidneys and intestines removed, the tilt reflex was still present. Dose‐response curves to l‐DOPA were the same as in normal animals. RO4‐4602 (3 mg/kg) prevented postural hypotension and block of the carotid occlusion pressor effect; supine hypotension was also observed after l‐DOPA.
The recovery response to tilting in spinal cats was markedly depressed or absent unless the blood pressure was elevated by angiotensin, in which experiments l‐DOPA depressed the recovery upon tilting (i.e. induced postural hypotension).
Blood pressure responses to tyramine were increased after 10 mg/kg of l‐DOPA, but depressed after 100 mg/kg. The response to tyramine was not depressed, however, when RO4‐4602 was given to block the dopa‐dopamine conversion.
The response to sympathetic stimulation in pithed rats was depressed after l‐DOPA and dopamine, but not after α‐methyldopa.
α‐Methyldopa (300 mg/kg) given acutely caused a moderate degree of postural hypotension and a more marked postural hypotension if given for two days.
It is concluded that it is possible to differentiate between the supine and postural hypotension caused by l‐DOPA and that supine hypotension is due to a central effect and postural hypotension to an extracerebral effect. Postural hypotension is discussed in relation to six hypotheses presented to explain its effect. Postural hypotension after l‐DOPA is probably not due to α‐adrenoceptor blockade, a central effect or any effect on the kidney. The most likely hypothesis is that l‐DOPA forms dopamine which acts as a false transmitter in the peripheral sympathetic nervous system.
Effect of inhibitors of γ‐aminobutyrate aminotransferase on the accumulation of H‐γ‐aminobutyric acid by the retina
Authors: NEAL M. J. , STARR M. S. 
Published: July 2012

Summary
Rat retinae pre‐incubated and incubated at 37° C in media containing amino‐oxyacetic acid (AOAA) (0·1 μm to 1 mm) accumulated more 3H‐γ‐aminobutyric acid (3H‐GABA) than control retinae incubated in the absence of AOAA. This increased accumulation of 3H‐GABA by tissue exposed to AOAA was not apparent at short incubation times (0–20 min), but became significant after incubations of 30 min, and maximal after incubation for 60 minutes.
At a concentration of 10 μm, AOAA did not alter the apparent Km for 3H‐GABA uptake or Vmax for either the low or the high affinity GABA uptake systems present in retina.
The potentiation of 3H‐GABA accumulation produced by AOAA appeared to parallel the inhibitory effect of this compound on 2‐oxoglutarate‐4‐aminobutyrate aminotransferase (GABA‐T). Similarly, hydrazinopropionic acid inhibited retinal GABA‐T and potentiated the accumulation of 3H‐GABA, but hydroxylamine and thiosemicarbazide which did not affect GABA‐T, were also without effect on the retinal accumulation of 3H‐GABA.
In vitro incubation with AOAA did not increase the endogenous levels of GABA or other amino acids in the retina.
AOAA did not significantly increase the retinal accumulation of radioactive l‐glutamate, l‐glutamine, taurine, glycine, α‐aminoisobutyrate or dopamine: the accumulation of l‐aspartate was increased by approximately 30%.
The inhibition of retinal GABA‐T by AOAA was time‐dependent and was not reversed by pyridoxal‐5′‐phosphate or by repeated washing of the tissue with fresh medium.
AOAA also inhibited glutamate decarboxylase (GAD) in retinae incubated in vitro. This inhibitory effect was partially reversed by pyridoxal‐5′‐phosphate.
Efflux of radioactivity from the retina was strikingly reduced in the presence of AOAA at concentrations sufficient to inhibit GABA‐T by 100%.
These findings suggest that AOAA potentiates the accumulation of 3H‐GABA by isolated retina, not by increasing the exchange of 3H‐GABA with the endogenous GABA pools, but by reducing the metabolism of the amino acid and hence reducing the loss of radioactivity from the tissue in the form of tritiated metabolites.
The distribution of lithium and its effects on the distribution and excretion of other ions in the rat
Authors: BIRCH N. J. , JENNER F. A. 
Published: July 2012

Summary
In rats, lithium (ca 1 mEquiv/kg body weight) decreased brain sodium and magnesium, bone sodium and calcium and increased muscle calcium, plasma magnesium, urinary calcium and urine volume.
Lithium was particularly concentrated in bone.
Effect of probenecid on the excretion of ampicillin in human bile
Authors: KAMPMANN J. , LINDAHL F. , HANSEN J. MØLHOLM , SIERSBÆK‐NIELSEN K. 
Published: July 2012

Summary
Ampicillin concentrations were determined in serum and bile after intravenous injection into patients with T‐tube bile drainage of 1 gram ampicillin before and during probenecid medication. The concentrations were followed up to fifteen hours after injection.
Probenecid increased the half‐life of ampicillin in serum from 74 minutes to 137 minutes.
Ampicillin concentrations in bile were higher following probenecid medication and a concentration over 5 μg/ml was obtained for 3 h longer than before probenecid.
The ampicillin concentrations in bile were approximately the same as those in serum both before and during probenecid medication suggesting passive transport of ampicillin from blood to bile.
A combined treatment of ampicillin and probenecid might be of clinical value in the therapy of cholangitis and typhoid carriers.
Rapid recovery of vascular adrenergic nerves in the rat after chemical sympathectomy with 6‐hydroxydopamine
Authors: FINCH L. , HAEUSLER G. , KUHN H. , THOENEN H. 
Published: July 2012

Summary
Twenty‐four hours after the last of 4 intravenous doses of 6‐hydroxydopamine (2×50 mg/kg on day 1 and 2×100 mg/kg on day 7) a complete impairment of adrenergic nerve function was observed in various organs of the rat.
A complete recovery of adrenergic nerve function in vascular smooth muscle was observed 7 days after the last dose of 6‐hydroxydopamine whilst in non‐vascular smooth muscle recovery took between 14 and 21 days.
On day 8, noradrenaline depletion produced by 6‐hydroxydopamine was not as great in vascular tissues, such as the mesentery and renal artery, as in other tissues, such as the heart and salivary glands. Noradrenaline concentrations recovered much more rapidly in vascular than in other tissues.
Electron microscope studies of small mesenteric arteries showed a complete destruction of adrenergic nerve terminals 24 h after 6‐hydroxydopamine (2×100 mg/kg). However, there was a reappearance of growing terminals within 7 days and after 28 days the regrowth of adrenergic nerve terminals seemed complete.
From the morphological and functional data it is concluded that 6‐hydroxydopamine does produce complete destruction of vascular adrenergic nerve terminals. However, these terminals regenerate more rapidly than those in other tissues. This could explain the failure of intravenously administered 6‐hydroxydopamine to prevent the development of experimental hypertension in the rat.
Effects of isoprenaline on contractions of directly stimulated fast and slow skeletal muscles of the guinea‐pig
Authors: TASHIRO N. 
Published: July 2012

Summary
The actions of isoprenaline on the contraction and the resting potential of the isolated extensor digitorum longus (EDL), a fast contracting muscle, and the soleus, a slow contracting muscle, of the guinea‐pig were investigated. Twitch tension was elicited by direct supramaximal stimulation and recorded isometrically.
The twitch tension of EDL elicited by pulses of 0·5–10 ms duration was increased in the presence of isoprenaline (1 μg/ml). Isoprenaline increased the twitch tension of the soleus elicited by a pulse of more than 5 ms duration, but decreased it when elicited by a pulse of less than 1 millisecond. These effects were blocked by propranolol (1–3 μg/ml) but not by phentolamine (1–5 μg/ml).
In EDL, isoprenaline prolonged the time to peak tension and the half‐relaxation time. The twitch of the soleus was shortened by isoprenaline due to an acceleration of relaxation. These findings were independent of stimulus duration.
The potentiating effects of isoprenaline on the twitch tension of EDL and the soleus were not observed in K+‐free Krebs solution and were abolished by ouabain (1 μg/ml) and by reduction of the temperature from 33° to 18° C. The effects of isoprenaline on the relaxation process were not affected by these treatments.
In EDL, the resting potential increased from 77·3 mV to 78·5 mV after isoprenaline, whereas in the soleus it increased from 691 to 74·7 mV. These effects were blocked by propranolol, K+‐deficiency, ouabain, and cooling to 18° C. Hyperpolarization by isoprenaline was increased by substitution of isethionate for the external chloride.
There was a good correlation between the potentiation of the mechanical response and the hyperpolarization of the membrane by isoprenaline. The hyperpolarization seems to be due to activation of the Na+‐K+ pump.
The effects of bretylium on the subcellular distribution of noradrenaline and on adrenergic nerve function in rat heart
Authors: ABBS E. T. , PYCOCK C. J. 
Published: July 2012

Summary
The effects of bretylium were investigated on the content and subcellular distribution of noradrenaline in the rat heart and on the response to stimulation of the sympathetic nerves supplying the heart.
In most experiments bretylium produced no change in the total noradrenaline content of the heart but significant changes were produced in the subcellular distribution of noradrenaline.
Treatment with amphetamine both prevented and antagonized the bretylium‐induced adrenergic neurone blockade and most of the accompanying changes in the subcellular distribution of noradrenaline.
There was a temporal correlation between the bretylium‐induced depletion of noradrenaline from the microsomal (P2) fraction and adrenergic neurone blockade.
The onset of adrenergic neurone blockade was also accompanied by an elevation of the noradrenaline content in the low‐speed coarse (P1A) fraction and in the mitochondrial (P1B) fraction; this elevation was prevented by pre‐treatment with α‐methyl‐p‐tyrosine.
It is concluded that although the elevation of the noradrenaline content of the P1a and P1B fractions and a depletion of amine from the P2 fraction are associated with the onset of adrenergic neurone blockade only the depletion from the P2 fraction is required for its maintenance. This conclusion supports the hypothesis that only a small portion of the noradrenaline content of an adrenergically‐innervated organ is associated with the release of transmitter, for when this small ‘store’ is depleted, by agents like bretylium, the nerves fail to function.
Assessment of selective β‐adrenoceptor blockade in man
Authors: BRIANT R. H. , DOLLERY C. T. , FENYVESI T. , GEORGE C. F. 
Published: July 2012

Summary
Selective antagonism of the cardiac β1‐adrenoceptors has been studied in normal human volunteers.
Practolol and UK 6558 produced greater antagonism of the chronotropic and inotropic responses to i.v. isoprenaline than of the vasodilator response to either i.v. or intra‐arterial isoprenaline. A third drug, M&B 17,803A, produced non‐selective β‐adrenoceptor blockade in 2 of 3 subjects studied.
Practolol, UK 6558 and M&B 17,803A, produced an attenuation of the responses to Valsalva's manoeuvre.
A substantial reduction in blood pressure was seen in 3 of 4 normotensive subjects given UK 6558.
Cardiovascular responses to noradrenaline in the rat before and after administration of various anaesthetics
Authors: BREZENOFF H. E. 
Published: July 2012

Summary
Cardiovascular responses to intravenously administered noradrenaline were monitored in the rat in the conscious state and again following anaesthesia. Injections and pressure recordings were made via permanently implanted venous and arterial catheters.
The pressor response to noradrenaline was inhibited by diethyl ether, urethane and deep pentobarbitone anaesthesia. It was unchanged by ketamine and was potentiated by chloralose and light pentobarbitone anaesthesia.
Reflex bradycardia was potentiated by chloralose, blocked by ketamine and reduced by pentobarbitone. It was either reduced or unchanged by ether or urethane.
The effect of cannabinoids on intestinal motility and their antinociceptive effect in mice
Authors: CHESHER G. B. , DAHL C. J. , EVERINGHAM M. , JACKSON D. M. , MARCHANT‐WILLIAMS H. , STARMER G. A. 
Published: July 2012

Summary
After oral administration to mice, pethidine, Δ8‐tetrahydrocannabinol (THC), Δ9‐THC, a cannabis extract and cannabinol had a dose‐dependent antinociceptive effect when measured by the hot‐plate method. Cannabidiol was inactive at 30 mg/kg. Δ8‐THC, Δ9‐THC and pethidine did not differ significantly in potency, but Δ9‐THC was 6·5 times more active than cannabinol.
After oral administration, three different cannabis extracts, Δ8‐THC, Δ9‐THC and morphine produced dose‐dependent depressions of the passage of a charcoal meal in mice. Δ8‐THC and Δ9‐THC were equipotent and were about five times less potent than morphine. Cannabidiol was inactive up to 30 mg/kg. The effect of the three cannabis extracts on intestinal motility could be accounted for by their Δ9‐THC content.
The antinociceptive effect of pethidine and the effect of morphine on intestinal motility were antagonized by nalorphine whilst the effects of the cannabis extracts and the pure cannabinoids were not.
From these results it is concluded that although cannabis and the narcotics share several common pharmacological properties, the mode of action of each is pharmacologically distinct.
VASCULAR REACTIVITY IN SPONTANEOUSLY HYPERTENSIVE NORMOTENSIVE AND HYPOTENSIVE RATS
Authors: DUPONT J. , SASSARD J. 
Published: July 2012

Three strains of rats spontaneously hypertensive (HRS), normotensive (NS) and hypotensive (HOS), were selected by repeated inbreeding.
In order to explain the different blood pressure levels observed, we have studied their vascular reactivity to noradrenaline and angiotensin II. Experiments were performed in anaesthetized ganglion‐blocked, vagotomized rats.
The reactivity to noradrenaline was significantly higher in HRS than in NS and HOS rats.
The reactivity to angiotensin II appeared identical in the three strains used.
EFFECTS OF MARIHUANA IN LABORATORY ANIMALS AND IN MAN
Authors: CARLINI E.A. , KARNIOL I.G. , RENAULT P. F. , SCHUSTER C.R. 
Published: July 2012

The pharmacological potencies of the resins from three different samples of Brazilian marihuana (A, B and C) were determined through corneal areflexia in rabbits, decrease of spontaneous motor activity and induction of catatonia in mice, and decrease of rope climbing performance of rats.
The Δ9‐tetrahydrocannabinol (Δ9 THC) content of the marihuanas, measured by gas chromatography, was 0.82, 2.02 and 0.52%, respectively, for samples A, B and C. Approximately 2% cannabinol was present in samples A and B whereas the content of cannabidiol was approximately 0.1%.
The petroleum ether extraction of the samples A, B and C yielded, respectively, 12.06, 14.56 and 4.26% of resin.
In all animal tests resin B was nearly twice as active as resin A, whereas C was the weakest.
The smoke of the marihuana samples was inhaled by 33 human subjects, under a double‐blind standardized procedure. Pulse rate, a time production task and an evaluation of psychological effects were recorded.
The smoke of 250 mg of sample B provoked disruption of the time production task, increased pulse rate, and induced strong psychological reactions in four of the six subjects who received it. Similar effects, although slightly smaller, were obtained with 500 mg of sample A. On the other hand, 500 mg of sample C did not differ from placebo.
It is suggested that it is possible by means of animal tests to predict the potency of a marihuana sample in man.
In parallel experiments, Δ9‐THC was administered to other human subjects and to laboratory animals in a manner similar to that in which the marihuana samples were administered.
Comparison of the results between the marihuanas and Δ9‐THC showed that in man and in the laboratory animals marihuanas A and B induced effects two to four times greater than expected from their Δ9‐THC content.
It is suggested that there may be potentiation of the effects of Δ9‐THC by other substances present in these marihuana samples.
THE INFLUENCE OF ANAESTHETICS ON THE INCREASE IN THE WATER PERMEABILITY OF THE TOAD BLADDER INDUCED BY VASOPRESSIN
Authors: GREY D. , ULLMANN ELISABETH 
Published: July 2012

Single lobes of the bladder of Bufo marinus were isolated and filled with, and suspended in, oxygenated Ringer solution. The fluid in contact with the outside (serosa) of the lobes had a total osmolarity of 225 m‐osmol/litre, and that bathing the inside (mucosa) of 45 m‐osmol/litre.
Osmotic water flow from mucosa to serosa was measured by weighing the lobes every 30 minutes. It was negligible unless vasopressin was added to the serosal bath. Standard concentrations of either 1.25 or 6.25 mu/ml were used to render the bladder lobes permeable to water.
The presence in the serosal medium of pentobarbitone or thiopentone in concentrations ranging from 0.25 to 2.5 mm, or of chloralose in concentrations ranging from 0.65 to 6.5 mm, diminished the increase in water permeability induced by vasopressin.
The three anaesthetics exerted similar inhibitory effects on the action of vasopressin from the serosal and from the mucosal surface of the bladder.
In the presence of a constant high concentration of anaesthetic, increasing the concentration of vasopressin over three orders of magnitude led to stepwise increases of osmotic water flow out of the lobes, although at every dose level the effect of vasopressin was depressed by the anaesthetic. However, it was not completely abolished even if the concentration of vasopressin was close to threshold.
The increase in water permeability of the bladder induced by 3′,5′‐adenosine monophosphate (cyclic AMP) was also depressed by the three anaesthetics.
Possible explanations of the findings are discussed.
THE BINDING OF [3H]‐PROPYLBENZILYLCHOLINE MUSTARD BY LONGITUDINAL MUSCLE STRIPS FROM GUINEA‐PIG SMALL INTESTINE
Authors: BURGEN A.S.V. , HILEY C.R. , YOUNG J.M. 
Published: July 2012

The synthesis of tritium labelled propylbenzilylcholine mustard ([3H]‐PrBCM; N‐2′‐chloroethyl‐N‐[2″, 3″‐3H2] propyl‐2‐aminoethyl benzilate) is described.
The uptake by muscle strips was measured and shown to be considerably increased by previous immersion of the muscle in distilled water.
A considerable part of the uptake is inhibited selectively by atropine, but not by nicotinic antagonists. A number of muscarinic agonists also inhibit uptake and their apparent affinity constants have been determined.
The uptake by atropine‐sensitive sites is temperature‐insensitive, whereas the other sites are temperature‐sensitive. Recovery is highly temperature‐sensitive and there is good agreement between recovery of sensitivity to agonists and loss of radioactivity from the muscle.