bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of cyclic 3′,5′‐AMP and other adenine nucleotides on the melanophores of the lizard (Anolis carolinensis)
Authors: HADLEY MAC E. , GOLDMAN JOEL M. 
Published: July 2012

. Cyclic 3′,5′‐AMP has been reported to darken skins of the frog, Rana pipiens. This suggests that cyclic 3′,5′‐AMP may mediate the action of MSH on amphibian chromatophores. Since MSH also darkens skins of the lizard, Anolis carolinensis, we investigated the effects of cyclic 3′,5′‐AMP and other nucleotides on Anolis melanophores to determine whether cyclic 3′,5′‐AMP may be the intracellular mediator of hormone action on melanophores of another vertebrate class.
. Cyclic 3′,5′‐AMP, itself, causes a rapid melanin granule aggregation within melanophores of Anolis. This response is, however, somewhat nonspecific in that both 5′‐ATP and 5′‐ADP also lighten the skins by aggregating the melanin granules. Another nucleotide, 5′‐AMP, darkens the skins by dispersing melanin granules. Cyclic 2′,3′‐AMP does not darken or lighten Anolis skins.
. Dibutyryl cyclic 3′,5′‐AMP, which is considered to be better able to penetrate membranes and resist degradation by a specific phosphodiesterase, maximally darkens Anolis skins, as does MSH. This darkening by the potent dibutyryl cyclic 3′,5′‐AMP suggests that cyclic 3′,5′‐AMP may be the intracellular mediator of melanin granule dispersion within Anolis melanophores leading to skin darkening.
. Other evidence supporting the first‐messenger—second‐messenger hypothesis for melanophore regulation is discussed.
. The differences in responses of Anolis melanophores to adenine nucleotides may relate to the ability of these agents to penetrate melanophore membranes; thus, the nucleotides could exert their effects either intracellularly or extracellularly on the plasma membrane.
Anti‐inflammatory activity of the steroid alkaloid glycoside, tomatine
Authors: FILDERMAN R. B. , KOVACS B. A. 
Published: July 2012

. Tomatine, isolated from extracts of crown gall‐infected tomato plants or obtained commercially, was tested for anti‐inflammatory activity using three different methods.
. Tomatine administered to intact rats intramuscularly in a dose range of 1–10 mg/kg or orally in doses of 15–30 mg/kg exerted a significant dose dependent inhibition of carrageenan induced paw oedema. The inhibitory effect of tomatine when given in a dose of 10 mg/kg intramuscularly to intact rats lasted more than 24 hr.
. In adrenalectomized rats significant dose‐related inhibition of paw oedema was obtained with tomatine and the inhibition at each dose level (0·5–10 mg/kg) was found to be greater than that found in intact animals.
. Tomatine administered subcutaneously to intact rats daily for 7 days in doses of 5 or 10 mg/kg exerted a significant, dose dependent inhibition of granulation tissue formation induced by the subcutaneous implantation of carrageenan impregnated cotton pellets.
. Tomatine administered to intact mice in a dose of 10 mg/kg subcutaneously 1 hr before the intraperitoneal injection of acidified saline and intravenous pontamine sky blue significantly decreased the leakage of the protein bound dye into the peritoneal cavity.
. Tomatidine, the aglycone of tomatine, was not effective at dose levels of 10–20 mg/kg in any of the three tests.
Pharmacological significance of biogenic amines in the lungs: histamine
Authors: AVIADO DOMINGO M. , SADAVONGVIVAD CHIRAVAT 
Published: July 2012

Summary
. Eight animal species were investigated for the histamine content of the lung and can be divided into two groups: the low‐level group, ranging from 2 to 7 μg/g, consisting of the mouse, rat, guinea‐pig and rabbit; and the high‐level group, ranging from 12 to 35 μg/g, consisting of the cat, dog, goat and human. In two species of the high‐level group (cat and dog) the amount of histamine that elicited an increase in pulmonary resistance was one‐fifth to one‐tenth of the dose that elicited an increase in species of the low‐level group (rat and rabbit). There is an inverse relationship between the content of histamine and the dose of histamine that produces a 25% increase in pulmonary resistance.
. Anaphylaxis increases the histamine content of the lung of the rabbit but not of the lung of the guinea‐pig. In both species, anaphylaxis is accompanied by an elevation of the concentration of 5‐hydroxytryptamine in the lung, indicating the trapping of platelets in the lung.
. The development of severe parasitaemia in the mouse inoculated with Plasmodium berghei is accompanied by an elevation of the histamine content of the lung. This increase appears to be part of the response of the lung to parasitaemia.
Actions of sarin on fast‐twitch and slow‐twitch skeletal muscles of the cat and protective action by anticholinergic drugs
Authors: BRIMBLECOMBE R. W. , EVERETT SALLY D. 
Published: July 2012

Summary. The organophosphate cholinesterase inhibitor sarin has been studied for its effects on the contraction of fast‐twitch (flexor hallucis longus, FHL) and slow‐twitch (soleus) muscles in the cat.. In both muscles lower doses (2·5 to 20 μg intra‐arterially) potentiated, and higher doses (20 μg and over) depressed, twitches produced by indirect stimulation. Muscle action potentials became repetitive. There was no simple relationship between degree of inhibition of blood cholinesterase and effect on muscle twitch.. The effects of the drug on repetitively stimulated muscles were dependent on both dose and frequency of stimulation. Doses of 2·5 to 10 μg increased the degree of fusion of low frequency tetani (10 Hz for FHL, 5 Hz for soleus) but depressed and caused non‐maintenance of tetani at high frequencies (150 Hz and above for FHL, 60 Hz and above for soleus). Doses of 20 μg and above depressed and caused non‐maintenance of tetani at all frequencies.. The anticholinergic drug N‐ethyl‐2‐pyrrolidylmethylcyclopentylphenyl glycollate (PMCG) injected intra‐arterially protected both muscles from the effects of sarin on twitch but less so from effects on tetani. When given after sarin the drug reversed twitch potentiation and repetitive firing. In contrast, atropine had little effect on the responses to sarin.. The effects of (+)‐tubocurarine were compared with those of PMCG.. The possible mode of action of PMCG is discussed.
Quantitative studies of the effect of antagonists on the acute toxicity of organophosphates in rats
Authors: NATOFF I. L. , REIFF B. 
Published: July 2012

Summary
. The subcutaneous acute toxicities of the vinyl phosphate pesticides mono‐crotophos, dicrotophos, chlorfenvinphos, crotoxyphos, dichlorvos, mevinphos, and of the experimental compounds SD 4455 (cis‐2‐carboxy‐1‐methylvinyl dimethylphosphate) and SD 7779 (cis‐2‐(1‐phenylethoxy) carbonyl‐1‐methylvinyl diethylphosphate) have been determined in female rats.
. The effects on the log dose‐probit mortality curves to the vinylphosphates of the therapeutic subcutaneous administration of methylatropine, atropine, N‐methylpyridinium‐2‐aldoxime methanesulphonate and obidoxime have been studied.
. Elevation of the LD50 values by the therapeutic regimens was shown to be an unsatisfactory measure of therapeutic efficiency, while reduction of the effect of a maximally lethal dose (LD90) to less than that of a minimally lethal dose (LD10) provided a better quantitative measure of therapeutic efficiency.
. The combination of atropine sulphate (50 μmol base/kg) with obidoxime (250 μmol/kg) was found to be generally the most effective of the antidotal regimens.The authors thank Mr. G. R. Ellender for his valuable technical assistance and Mr. D. L. Holmes, of the Statistics Unit of the Woodstock Agricultural Research Centre, for the statistical evaluations incorporated in this work.
The action of ranatensin, a new polypeptide from amphibian skin, on the blood pressure of experimental animals
Authors: GELLER R. G. , GOVIER W. C. , PISANO J. J. , TANIMURA T. , VAN CLINESCHMIDT B. 
Published: July 2012

Summary
. The blood pressure response to ranatensin, an undecapeptide from the skin of the frog, Rana pipiens, has been studied in various experimental animals.
. Ranatensin raised blood pressure in the dog and rabbit. The response was not altered by atropine, phentolamine, propranolol or hexamethonium, suggesting a direct peripheral vasoconstrictor action. In both animals ranatensin was about one‐tenth as potent as angiotensin. Tachyphylaxis to ranatensin did occur, but there was no cross‐tachyphylaxis with angiotensin, bradykinin, or noradrenaline.
. The peptide lowered blood pressure in the monkey, being as potent as eledoisin. The response was not altered by atropine, phentolamine, propranolol, tripelennamine, tetraethylammonium, bretylium, or methysergide. This again suggests a direct peripheral action on vascular smooth muscle. There was no tachyphylaxis to the depressor action, nor was there cross‐tachyphylaxis with angiotensin, eledoisin, bradykinin, or noradrenaline.
. Ranatensin did not alter the blood pressure in cats and had a variable action in the guinea‐pig with a rapid onset of tachyphylaxis.
. Ranatensin has a variable effect on the blood pressure in the rat that is related to the basal level of blood pressure. When the blood pressure is high, the response to the peptide is hypotension. Ranatensin raises blood pressure in the rat when the basal blood pressure is low. The pressor response to ranatensin appears to be due, in part, to the release of noradrenaline from peripheral sympathetic nerve endings.
. The composite action of ranatensin on blood pressure of various experimental animals is unlike that of any other peptide. Its hypertensive action in the dog or rabbit, together with a potent hypotensive action in the monkey, readily distinguishes it from all other vasoactive peptides.
The effect of parachlorophenylalanine on the behaviour of cats
Authors: HOYLAND VALERIE J. , SHILLITO ELIZABETH E. , VOGT MARTHE 
Published: July 2012

Summary
. Male and female kittens and adult cats were given p‐chlorophenylalanine orally.
. After treatment, some of the male cats showed mounting behaviour and the kittens and non‐oestrous females showed an increase in treading and rubbing which was similar to one aspect of pro‐oestrus behaviour.
. The treated animals also appeared to suffer from skin irritation and showed increased restlessness which accompanied sleep deprivation.
. Injection of 5‐hydroxytryptophan stopped abnormal sexual activity and restored normal sleep for about 5 hours.
. It is concluded that 5‐hydroxytryptamine‐containing neurones inhibit sexual behaviour in cats and that this role can be seen in male and, to some extent, also in female animals.
Actions of bretylium tosylate at the neuromuscular junction
Authors: FERRY G B. , NORRIS BERYL 
Published: July 2012

Summary
The actions of bretylium tosylate on neuromuscular transmission in the rat phrenic nerve diaphragm preparation have been investigated by electrophysiological methods. Additional experiments have been made on the effect of the drug on the frog rectus preparation and on the acetylcholinesterase of erythrocytes.
After bretylium, there was a reduction in the amplitudes of miniature endplate potentials (mepps), endplate potentials (epps) and acetylcholine potentials recorded in the diaphragm, and also in the contractures of the rectus in response to acetylcholine (ACh) and to carbachol.
After bretylium, there was a prolongation of the time courses of epps and ACh potentials. Under certain circumstances there was enhancement of the amplitudes of epps and ACh potentials and of the contractile responses to ACh but not to carbachol.
Bretylium reduced the velocity of hydrolysis of ACh by erythrocyte ghosts. This inhibition was competitive and the Ki of bretylium was 0·053 mm.
Bretylium did not cause a reduction in the mean quantal content of the epp in junctions blocked with Mg++.
It is concluded that bretylium exerts both facilitatory and inhibitory influences on neuromuscular transmission, which, exerted simultaneously, may give the false appearance that the drug has little action at this synapse.
Plasma concentration, uptake by liver, and biliary excretion of tritiated cardiac glycosides in the isolated perfused guinea‐pig liver
Authors: KOLENDA K.‐D. , LÜLLMANN H. , PETERS T. , SEILER K.‐U. 
Published: July 2012

Summary
Investigations were carried out on isolated perfused guinea‐pig livers. Different doses of tritiated ouabain, digoxin, and digitoxin were added to the perfusion medium and the subsequent plasma elimination, hepatic uptake, and biliary excretion quantitatively measured. After the perfusion, extracts of liver, bile and plasma were subjected to thin layer chromatography in order to detect the radioactively labelled glycosides and their metabolites.
The ouabain concentration in the plasma approached the equilibrium stage within 45 minutes. At this time 40% of the administered dose had been taken up by the liver, and no further elimination occurred. The elimination curve for ouabain followed a simple exponential function. After 1 h the tissue medium (T/M) ratio was approximately 3. In bile hardly any radioactivity could be detected. Ouabain was therefore not excreted by the liver.
Up to 80% of the digitoxin was eliminated from the plasma within 4 hours. The elimination of radioactive material for the dose range studied could be described by a hyperbolic function. The T/M ratio in the liver varied with time. At the beginning it was as high as 10 and after 4 h reduced to approximately 3. After 45–60 min the concentration of radioactive material in the bile was 500 times as high as that in the plasma. Almost 70% of the administered radioactivity was excreted with the bile within 4 hours. At the end of the perfusion almost all the identifiable substances in plasma and bile were polar metabolites, as shown by thin layer radiochromatography.
Digoxin behaved similarly to digitoxin.
The findings led to the following hypothesis: uptake of cardiac glycosides into the liver cells occurs by a passive diffusion process and is related to their lipid solubility. On the other hand excretion in the bile occurs in general if polar metabolites are formed in the liver cells.
Metabolism of cardiac glycosides studied in the isolated perfused guinea‐pig liver
Authors: KOLENDA K.‐D. , LÜLLMANN H. , PETERS T. 
Published: July 2012

Summary
Metabolic degradation of tritiated ouabain, digoxin, and digitoxin has been investigated quantitatively using the isolated perfused guinea‐pig liver. The cardiac glycosides and their metabolites have been extracted from the plasma, liver, and bile by different solvents and identified as far as possible by radio‐chromatographic analysis.
The total metabolic activity in the experimental system was localized in the liver.
The hydrophilic glycoside ouabain could not penetrate into the metabolically active compartment of the liver and was, therefore, not degraded. The more lipophilic compound digitoxin, however, was completely degraded due to its high affinity for the metabolically active sites. The unchanged digitoxin cannot enter the aqueous bile fluid in contrast to its more hydrophilic metabolites.
The only detectable metabolic degradation of digoxin was a conjugation with glucuronic and/or sulphuric acid, but a cleavage of sugar molecules seemed not to occur.
In the case of digitoxin the metabolic processes are more complicated: sugar cleavage, conjugation, and C‐12 hydroxylation take place simultaneously. An immediate hydroxylation of digitoxin leading to digoxin was not observed. After administration of digitoxin conjugation products as well as digoxigeninbis‐and digoxigenin‐mono‐digitoxosides were present in each of the compartments investigated, but the digitoxosides of digitoxigenin were intermediates in concentrations too low to be determined indicating a very high rate of conjugation and/or C‐12 hydroxylation as compared with the cleavage of the digitoxoses.
A scheme for the metabolic pathways of the cardiac glycosides based on experimental results is presented. The metabolic behaviour of each of the three compounds involved is closely related to their physicochemical properties, especially the lipid solubility.
Importance of noradrenaline found in a functional pool in maintaining spontaneous locomotor activity in rats
Authors: ONN‐LENG CHAN , WEBSTER R. A. 
Published: July 2012

SummarySpontaneous locomotor activity (activity) in male Wistar rats was compared with the concentrations of brain noradrenaline (NA), dopamine (DA) and metaraminol.α‐Methyl‐m‐tyrosine (αMMT) (400 mg/kg) reduced the concentrations of DA as well as NA but activity remained high in the presence of metaraminol formed from the αMMT. When tetrabenazine (TBZ) was given after αMMT pretreatment there was a fall in the levels of activity and in the concentrations of NA, DA and metaraminol.α‐Methyl‐p‐tyrosine (αMT) produced a fall in activity which was correlated with falls in the concentrations of NA and DA. 5‐Hydroxytryptamine (5‐HT) did not appear to be affected.After depletion of NA and DA by αMT and TBZ, administration of L‐dopa produced a return in activity which was significantly correlated with the concentration of NA but not DA. When αMMT was given to a similar group of pretreated animals there was no recovery of activity despite high concentrations of DA and metaraminol.The dopamine β hydroxylase inhibitor, diethyldithiocarbamate (DDC), suppressed activity as well as the concentrations of NA and DA at high doses (750 mg/kg) but smaller doses (400 mg/kg) plus L‐dopa gave high DA concentrations without activity.It is concluded that NA and not DA is associated with activity but that it is only part of the total NA which is in the biosynthetic storage granule affected by drugs like αMT and TBZ, which controls activity. Drugs that do not affect this pool may lower NA concentrations but not reduce activity.The replacement of NA by metaraminol in this functional pool does not restore activity.
Cardiovascular pharmacology of quazodine (MJ‐1988), with particular reference to effects on myocardial blood flow and metabolic heat production
Authors: PARRATT J. R. , WINSLOW EILEEN 
Published: July 2012

Summary
The effects of intravenous infusions of quazodine (6,7‐dimethoxy‐4‐ethyl‐quinazoline; MJ‐1988) on myocardial blood flow, myocardial metabolic heat production and on general haemodynamics have been studied in cats anaesthetized with sodium pentobarbitone.
Quazodine (0·25 and 0·5 (mg/kg)/min for 10 min) decreased diastolic blood pressure, peripheral vascular resistance, systolic ejection time and left ventricular end‐diastolic pressure. Heart rate, cardiac effort, output and external work and left ventricular dP/dt were markedly increased. These changes are indicative of increased myocardial contractility and peripheral vasodilatation.
In a dose of (1·0 mg/kg)/min, quazodine had a more marked hypotensive effect, systolic pressure being significantly reduced, and had less effect on left ventricular dP/dt and cardiac effort. Calculated external cardiac work was slightly reduced and there were very occasional nodal arrhythmias.
Changes in heart rate, aortic dP/dt and diastolic blood pressure induced by quazodine were unaffected by the previous administration of the β‐adrenoceptor blocking agent alprenolol in a dose (1·0 mg/kg) which abolished the effects of isoprenaline.
In all doses, quazodine markedly increased local blood flow (by 70–540%) around an implanted myocardial heated thermocouple recorder. ‘Corrected temperature’, an index of local myocardial metabolic heat production, was almost unchanged and it is suggested that increased myocardial contractility, occurring with unchanged metabolic heat production and oxygen consumption, probably results from a concomitant decrease in intramural wall tension.
3,4‐Dihydroxyphenylacetic acid and 4‐hydroxy‐3‐methoxyphenylacetic acid in the mouse striatum: a reflection of intra‐ and extra‐neuronal metabolism of dopamine?
Authors: ROFFLER‐TARLOV SUZANNE , SHARMAN D. F. , TEGERDINE P. 
Published: July 2012

Summary
The administration of probenecid to mice increased the concentration of 4‐hydroxy‐3‐methoxyphenylacetic acid (HVA) in the striatum, but did not raise the concentration of 3,4‐dihydroxyphenylacetic acid (DOPAC).
After drug treatments which normally increase the concentration of HVA several‐fold, inhibition of catechol‐O‐methyltransferase (COMT) by tropolone greatly reduced the concentration of HVA but resulted in only a small increase in the concentration of DOPAC in the striatum of the mouse.
These results indicate that HVA and DOPAC do not occur at the same location in the tissue of the striatum and that DOPAC is not normally metabolized to HVA to any great extent in this tissue.
When mice were treated with reserpine, which is thought to prevent the intraneuronal storage of dopamine, there was an increase in the striatal concentration of DOPAC which preceded an increase in the concentration of HVA. Since non‐cholinergic nerve endings of rat brain contain mitochondria and show monoamine oxidase activity, this result suggests that DOPAC is formed intraneuronally.
It is concluded that the DOPAC in the striatum represents intraneuronal metabolism of dopamine and that only the HVA which is sensitive to the action of probenecid represents entirely extraneuronal metabolism of this amine. Some of the HVA is not sensitive to the action of probenecid. This suggests that part of the metabolism of dopamine involves both locations.
A group of drugs which are chemically related to amphetamine were tested for their effects on the concentrations of DOPAC and HVA in the striatum. It is suggested that d‐amphetamine, 2‐aminotetralin and 1,2,3,4‐tetrahydroisoquinoline reduced the intraneuronal metabolism of dopamine whereas adamantanamine did not.
Mediators of the inflammation induced in the rat paw by carrageenin
Authors: CRUNKHORN PEARL , MEACOCK S. C. R. 
Published: July 2012

Summary
The time course of oedema formation in rats caused by injection of carrageenin into the paw was followed for 5·5 hours. Intact or adrenalectomized rats which had previously been injected with ellagic acid or saliva to reduce considerably the concentration of blood kininogens, or with methysergide to antagonize 5‐hydroxytryptamine (5‐HT) showed a reduced inflammatory response. It was concluded that kinins and 5‐HT contributed significantly to oedema formation during this period.
Mepyramine alone had no effect on oedema formation, but in combination with ellagic acid treatment, with or without methysergide, it caused a reduction suggesting that histamine played a minor role in oedema formation during the first 3 hours.
Vascular permeability studies indicated that injection of ellagic acid did not interfere with the normal responses in skin to intradermal injections of histamine, 5‐HT, bradykinin or compound 48/80. Mepyramine and methysergide, at the doses used in the carrageenin experiments, completely antagonized histamine and 5‐HT, respectively, and did not affect the skin responses of bradykinin.
Treatment in vivo with ellagic acid or rat saliva was equally effective in reducing plasma kininogen concentrations by an amount equivalent to more than 10 times the quantity of substrate 1 measured by Gautvik & Rugstad (1967).
Rat saliva, but not ellagic acid, lowered complement levels by approximately 20%.