bluuebunny/crossref_metadata_2025 huggingface dataset:
HYDROLYSIS OF NEOSTIGMINE BY PLASMA CHOLINESTERASE
Authors: NOWELL P. T. , SCOTT CAROL A. , WILSON A.
Published: July 2012

Incubation of neostigmine with normal human plasma in vitro results in the formation of two quaternary nitrogen compounds, one of which has been identified as m‐hydroxyphenyltrimethylammonium. This hydrolysis is prevented by prior addition of dyflos to plasma in concentrations sufficient to inhibit plasma cholinesterase activity. The significance of these findings is discussed in relation to the occurrence of the same metabolic products in the urine of patients with myasthenia gravis treated with oral neostigmine. No equivalent findings are available for normal subjects since it was not considered justifiable to treat them with neostigmine.
SYMPATHETIC VASODILATATION IN THE RABBIT EAR
Authors: HOLTON PAMELA , RAND M. J.
Published: July 2012

Changes in the blood content of a 1 cm2 portion of the intact rabbit's ear were studied with transillumination and a photocell. Stimulation of the post‐ganglionic sympathetic nerves produced a decrease in blood content, attributable to vasoconstriction, followed by an increased blood content, attributable to vasodilatation. The vasodilatation was enhanced by eserine and decreased by atropine. Guanethidine abolished the vasoconstriction but not the vasodilatation. After the ganglion had been decentralized by degeneration of the pre‐ganglionic sympathetic nerves the vessels had an increased sensitivity to acetylcholine and the vasodilatation in response to sympathetic stimulation was enhanced. It is concluded that sympathetic stimulation results in the liberation of acetylcholine which causes vasodilatation.
NORADRENALINE CONTENT IN THE HEART AND SPLEEN OF THE MOUSE UNDER NORMAL CONDITIONS AND AFTER ADMINISTRATION OF SOME DRUGS
Authors: SHARMAN D. F. , VANOV S. , VOGT MARTHE
Published: July 2012

The noradrenaline content of the heart and spleen was investigated in normal mice and in mice treated with drugs. A modification of the methods of Bertler, Carlsson & Rosengren (1958) was used for extraction, and of v. Euler & Floding (1955) for fluorimetric estimation of the amine. In normal mice the mean noradrenaline content of the heart was 0.55 μg/g and that of the spleen 0.26 μg/g fresh tissue. Iproniazid (100 mg/kg), nicotine (0.1 mg/kg) and histamine (0.5 mg/kg), given 1 and 3 hr before killing the mice, did not significantly change the concentration of noradrenaline in the heart. Neither did nicotine and histamine, administered 1 hr before death, significantly alter the noradrenaline content of the spleen. The rapid changes in the catechol amine content of mouse tissues reported with these drugs by De Schaepdryver & Preziosi (1959) were not observed. In contrast, reserpine (2.5 mg/kg), methyl reserpate methyl ether (1 mg/kg), and methyl 18‐epireserpate methyl ether (2 mg/kg) caused severe depletion of noradrenaline from the heart and spleen of the mice.
CHOLINERGIC TRANSMISSION IN THE FROG SPINAL CORD
Authors: MITCHELL J. F. , PHILLIS J. W.
Published: July 2012

The effect of acetylcholine and other drugs has been tested on the isolated and sagittally hemisected spinal cord of the frog (Rana temporaria). The release of acetylcholine from this preparation during stimulation of the spinal roots and whole hemicord has also been studied. After inactivation of the tissue cholinesterases acetylcholine was released spontaneously from the preparation at a steady rate of about 5.5 pmole/15 min/preparation. No increase in this release was obtained by stimulating the dorsal roots, but antidromic stimulation of the ventral roots always gave an increase in the rate of acetylcholine release up to 2.3 times the spontaneous level. Direct stimulation of the spinal cord did not alter the rate of acetylcholine release. Acetylcholine (1 mm) and eserine (10 mm) had weak excitatory actions and prolonged the reflex response of the preparation during dorsal root stimulation, but dihydro‐β‐erythroidine and atropine had no effect. The response evoked by antidromic ventral root stimulation was potentiated by eserine (10 μm) and depressed by acetylcholine (10 μm) and dihydro‐β‐erythroidine (1 μm) as in the toad preparation. The evidence supporting cholinergic transmission at some synapses in the spinal cord is discussed in relation to these results.
STIMULUS FREQUENCY AND NEUROMUSCULAR BLOCK
Authors: BLACKMAN J. G.
Published: July 2012

Muscle twitches of the rat isolated diaphragm and frog sartorius preparations were recorded. It was confirmed that, in the presence of tubocurarine, the degree of neuromuscular block was greater the higher the frequency of stimulation. The results suggest that the quantity of acetylcholine released by each nerve impulse was reduced by increasing the rate of stimulation so that, in a tubocurarine solution, muscle fibres which were only just being fired at a slow rate of stimulation failed to fire at a faster rate.
THE ADRENERGIC MECHANISM IN THE NICTITATING MEMBRANE
Authors: BURN J. H. , RAND M. J. , WIEN R.
Published: July 2012

The contractions of the nictitating membrane in response to postganglionic nerve stimulation have been studied in experiments in which cats' heads were perfused. When eserine was added to the perfusion fluid there was a rapid increase in the size of the contractions. In the presence of eserine the contractions produced by injecting acetylcholine into the perfusion fluid were greatly increased. When atropine was injected into the perfusion fluid the contractions caused by postganglionic nerve stimulation returned to the size before eserine was added. In experiments with cats anaesthetized with chloralose, atropine or hyoscine was given first and the effect of esdrine on the response to submaximal postganglionic nerve stimulation was determined. Eserine slowly increased the responses to stimulation without increasing the contraction produced by injecting noradrenaline. In other experiments in which maximal stimuli were used, the relation of stimulus frequency to height of contraction was determined. The optimal frequency was low, being 5 to 10 shocks/sec. In the presence of hyoscine, eserine or neostigmine increased the response to stimulation; this increase was greater at lower frequencies, and lessened as the frequency rose to the optimal value.
THE ASSAY OF CORTICOTROPHIN IN HYPOPHYSECTOMIZED AND IN HYDROCORTISONE‐TREATED RATS
Authors: ASHFORD A. , JONES J. I. M.
Published: July 2012

Twenty‐one pairs of parallel assays of corticotrophin are reported, in which results from hypophysectomized rats are compared with those from hydrocortisone‐treated animals. The two methods show little difference in respect of potency, precision and limits of error.
UPTAKE OF 5‐HYDROXY[14C]TRYPTOPHAN BY RAT AND DOG BRAIN SLICES
Authors: SMITH S. E.
Published: July 2012

Slices of rat brain take up and concentrate 5‐hydroxy[14C]tryptophan when incubated at 37° C in vitro. Uptake is inhibited by methyldopa and L‐phenylalanine in a competitive manner. Only a small proportion of the 5‐hydroxy[14C]tryptophan taken up is decarboxylated. This observation, and the lack of correlation between the effects of various amino‐acid inhibitors on uptake and on decarboxylase, suggest that the two processes are not linked. In the cold some passive diffusion of the amino‐acid occurs, as is thought to take place also at 37° C. Experiments with dog brain show that uptake varies from one part of the brain to another, being greatest in the caudate nucleus. The possible implications of the uptake mechanism in the treatment of animals or patients with large doses of amino‐acids are discussed.
ASYNCHRONOUS POSTGANGLIONIC FIRING FROM THE CAT SUPERIOR CERVICAL SYMPATHETIC GANGLION TREATED WITH NEOSTIGMINE
Authors: TAKESHIGE C. , VOLLE R. L.
Published: July 2012

Neostigmine injected intra‐arterially to the superior cervical ganglion of the cat evoked an asynchronous postganglionic nervous discharge in both normal and denervated superior cervical ganglia. This asynchronous firing was enhanced by tubocurarine but blocked by small doses of atropine. In addition, the responses evoked by acetylcholine in ganglia treated with neostigmine were characterized by two components. The first was blocked by tubocurarine and the second by atropine. Asynchronous firing evoked by repetitive preganglionic nerve stimulation of ganglia treated with neostigmine was blocked by atropine but not tubocurarine. It is suggested that neostigmine (1) has actions on ganglia other than those attributable to inactivation of cholinesterase, (2) may possess both pre‐ and post‐synaptic sites of action, and (3) may unmask a cholinoceptive site which can be blocked by atropine.
ACTION OF SYMPATHOMIMETIC DRUGS ON THE ISOLATED JUNCTION OF THE BILE DUCT AND DUODENUM
Authors: CREMA A. , BERTÉ F.
Published: July 2012

The actions of adrenaline, noradrenaline and phenylephrine were studied both on the terminal tract of bile duct (prepared as spiral strips or intact) and on the adjacent duodenum taken from the calf and the cat. These amines contract the terminal bile duct and relax the duodenum. Furthermore, on the basis of the action of some adrenaline antagonists, the hypothesis is advanced that there are α‐receptors which mediate contraction of muscle in the sphincterial zone of the bile duct.
SENSITIVITY TO DRUGS OF AUSTRALIAN LEPTOSPIRAL SEROTYPES
Authors: SPRADBROW P. B.
Published: July 2012

The in vitro susceptibilities to antibiotics of stock strains of various Australian leptospiral serotypes were established. Leptospira pomona was highly susceptible to penicillin and erythromycin, susceptible to streptomycin and tetracyclines, but resistant to chloramphenicol and novobiocin. In general, the twelve serotypes tested were susceptible to streptomycin, penicillin and tetracycline, but L. icterohaemorrhagiae, L. canicola and L. zanoni were more resistant than the other serotypes, especially to penicillin. A newly isolated strain of L. zanoni was more sensitive to penicillin, streptomycin, and tetracycline than was the stock strain. Against L. australis high concentrations both of penicillin and of streptomycin were bactericidal. In lower concentrations penicillin was bacteriostatic. In high concentrations penicillin caused lysis of leptospirae, but streptomycin and the tetracyclines did not. These results do not agree well with those on the chemotherapy of experimental infections.
THE SUBCELLULAR DISTRIBUTION OF HISTAMINE, SLOW‐REACTING SUBSTANCE AND 5‐HYDROXYTRYPTAMINE IN THE BRAIN OF THE RAT
Authors: CARLINI E. A. , GREEN J. P.
Published: July 2012

Various extracts of brain were prepared with dilute and concentrated acid, acetone and n‐butanol. When the extracts were applied to the guinea‐pig isolated ileum, they produced a slow contraction which was not prevented by an antihistamine; in addition, the acid and acetone extracts inhibited the action of histamine. Histamine in extracts of brain was separated from other pharmacologically active substances by chromatography on a carboxylic‐acid resin and estimated biologically. The bulk of this histamine was found in small particulate material, whereas slow‐reacting substance was found in particulate material of greater density. 5‐Hydroxytryptamine was in both the small and large particles. There was no relationship between the distribution of these substances and that of succinic dehydrogenase activity. The measurement of histamine in brain both by biological assay on the guinea‐pig ileum and by chemical assay using a fluorimetric procedure gave mean values of 53 and 246 ng/g of wet tissue, respectively. The high values obtained by the chemical assay are attributable in part to substances other than histamine which become fluorescent after reaction with o‐phthalaldehyde in this procedure.
OBSERVATIONS UPON ROLES OF ETHER OXYGEN, ALKYL GROUP SIZE, NUMBER OF ONIUM CENTRES AND INTERONIUM DISTANCE UPON NEUROMUSCULAR BLOCK IN BIS‐ AND POLYONIUM COMPOUNDS
Authors: LEWIS J. J. , MARTIN‐SMITH M. , MUIR T. C. ,   With the technical assistance of P. Leitch
Published: July 2012

Using the method of Van Rossum & Ariëns (1959), a number of bis‐, tris‐ and tetra‐onium neuromuscular blocking agents have been classified into depolarizing, non‐depolarizing and intermediate‐acting compounds. This investigation confirmed the results of experiments using conventional techniques. The role of the ether oxygen link, the effects of inter‐onium distance, alkyl group size and the number and nature of the onium groups were also investigated, and the reasons underlying the observed quantitative and qualitative differences discussed.
ANTAGONISM BY MEFENAMIC AND FLUFENAMIC ACIDS OF THE BRONCHOCONSTRICTOR ACTION OF KININS IN THE GUINEA‐PIG
Authors: COLLIER H. O. J. , SHORLEY PATRICIA G.
Published: July 2012

In the guinea‐pig, N‐(2,3‐xylyl)anthranilic acid (mefenamic acid) and N‐(α,α,α‐trifluoro‐m‐tolyl)anthranilic acid (flufenamic acid), two new anti‐inflammatory agents, antagonize bronchoconstriction, but not hypotension, produced by kinins. They do not reduce bronchoconstrictor responses to acetylcholine, histamine or 5‐hydroxytryptamine. The antibradykinin potencies of mefenamic and flufenamic acids approximately equal that of acetylsalicylic acid when given intravenously and of phenylbutazone when given into the duodenum. After administration of mefenamic and flufenamic acids, the bronchoconstrictor response can be restored by higher doses of bradykinin. The quantitative relationship between the intravenous dose of sodium mefenamate or flufenamate and the dose of bradykinin needed to surmount either antagonist in bronchial muscle fulfils the requirements for competitive antagonism. Antagonism by calcium acetylsalicylate can also be surmounted with higher doses of bradykinin, but in this instance the relationship of antagonist to agonist fulfils requirements for competitive antagonism only at the lower part of the dose range.
ULTRASTRUCTURAL CHANGES PRODUCED IN THE RAT KIDNEY BY A MERCURIAL DIURETIC (MERALLURIDE)
Authors: SANABRIA A.
Published: July 2012

Electron microscopic study of the cortical and medullary zones of kidneys of rats injected intraperitoneally with meralluride (a mercurial diuretic) shows that constant structural changes occur in the proximal tubules, but that the distal tubules remain unaltered. In the cells of the proximal tubule vacuolation and loss of contrast of the apical pole occur due to intracytoplasmic oedema, appearances which may extend as far as the basal pole. The brush border shows separation of the villi at the level of the implantation base. Mitochondrial swelling occurs with vacuolation of the matrix and disappearance of the cristae. The changes at the level of the glomerulus are variable and consist of clearing of the mitochondrial matrix of the podocytes, enlargement of the vesicles of the endoplasmic reticulum and the occurrence of intracytoplasmic osmiophilic masses.
ON THE NATURE OF THE CHEMICAL MEDIATORS INVOLVED IN ANAPHYLACTIC REACTIONS IN MICE
Authors: HALPERN B. N. , NEVEU T. , SPECTOR S.
Published: July 2012

The effects of mepyramine, promethazine, chlorpromazine and lysergic acid diethylamide have been compared on the capillary permeability changes of the skin, produced by histamine, by 5‐hydroxytryptamine and by passive cutaneous anaphylaxis in mice. Promethazine, mepyramine and chlorpromazine can inhibit, in decreasing order of activity, the effect of histamine, whilst lysergic acid diethylamide is inactive. Lysergic acid diethylamide and chlorpromazine are equally potent inhibitors of the action of 5‐hydroxytryptamine on the peripheral vascular bed, whilst mepyramine is inactive. Promethazine has intermediate activity. Passive cutaneous anaphylaxis is strongly inhibited by chlorpromazine and by promethazine. Mepyramine and lysergic acid diethylamide, each injected alone, affect only weakly the anaphylactic reaction. However, passive cutaneous anaphylaxis is almost completely abolished by the simultaneous injection of the two last antagonists. It is suggested that the anaphylactic reaction in mice is the result of simultaneous release of both mediators, histamine and 5‐hydroxytryptamine, each of them strengthening the effect of the other.
THE ACTION OF DRUGS ON THE CIRCULAR MUSCLE STRIP FROM THE GUINEA‐PIG ISOLATED ILEUM
Authors: HARRY J.
Published: July 2012

The circular muscle strip is a new preparation for examining the action of drugs on the circular muscle of the guinea‐pig isolated intestine. The preparation differed from the longitudinal muscle in that it was insensitive to drugs which act on autonomic effector tissues but, after inhibition of cholinesterase, it responded readily to choline esters, 5‐hydroxytryptamine, histamine and nicotine. This behaviour necessitated the treatment of each strip with the anticholinesterase NN‐diisopropylphosphodiamidic fluoride (mipafox) before each experiment. The contractions of the strip by 5‐hydroxytryptamine, histamine and nicotine were abolished by procaine, botulinum toxin (Type A), morphine and hemicholinium, whilst the actions of acetylcholine and methacholine were unaffected. Contractions of the strip in response to each of the drugs were abolished by atropine and hyoscine. The action of nicotine was specifically antagonized by hexamethonium, that of 5‐hydroxytryptamine by desensitization of the tissue to 5‐hydroxytryptamine, and that of histamine either by desensitization of the tissue to histamine or by mepyramine. It is postulated that 5‐hydroxytryptamine, histamine and nicotine stimulate specific receptor sites within the intramural nerve plexuses of the guinea‐pig isolated ileum. Finally, botulinum toxin (Type A), morphine or hemicholinum, acting on the neuronal elements of the intramural plexuses, depressed the contractions of the circular muscle strip due to histamine or nicotine more readily than those due to 5‐hydroxytryptamine.
THE ACTION OF ELEDOISIN ON THE SYSTEMIC ARTERIAL BLOOD PRESSURE OF SOME EXPERIMENTAL ANIMALS
Authors: ERSPAMER V. , GLAESSER A.
Published: July 2012

The blood pressure response following parenteral administration of eledoisin varies conspicuously from one animal species to another. In the dog the polypeptide elicits a clear hypotension under all experimental conditions. Eledoisin is active at extremely low dose levels and hypotension is not appreciably affected by previous treatment with atropine, sympatholytic drugs, ganglion‐blocking agents or reserpine. Eledoisin potently antagonizes the pressor effects of catechol amines and of angiotensin. Long‐lasting hypotension can be obtained by intravenous infusion or subcutaneous injection of the polypeptide. The mechanism of action of eledoisin in the dog is believed to be chiefly peripheral. The rabbit, the guinea‐pig and the cat behave like the dog in the type but not in the intensity of their blood‐pressure response to eledoisin. The rat gives variable responses to the polypeptide. After treatment with a ganglion‐blocking drug, or in the pithed rat, a rise in blood pressure is the predominant effect. In the anaesthetized chicken eledoisin generally produces a diphasic response, but in the decapitated animal only hypertension. This last effect is believed to depend largely, if not entirely, on the release of catechol amines from body stores. The dog blood pressure may be used for the assay of eledoisin; suitable results may also be obtained from the pressor effects in decapitated chickens.
INTERACTIONS BETWEEN COCAINE, TYRAMINE AND NORADRENALINE AT THE NORADRENALINE STORE
Authors: FARRANT J.
Published: July 2012

In the cat, the pressor actions of noradrenaline and of adrenaline were generally reduced and that of tyramine was increased during infusions either of noradrenaline or of adrenaline. The increase in the response to tyramine after an infusion of noradrenaline was prevented by cocaine, methyl phenidate and pipradrol. Pipradrol, unlike its isomer azacyclonol, increased the responses to catechol amines but reduced that to tyramine. Cocaine did not prevent the increase in the noradrenaline content of cat kidney and uterus after an infusion of noradrenaline. In the pithed rat, cocaine increased the pressor response to noradrenaline but antagonized that to tyramine. Treatment of the rat with reserpine prevented the effect of cocaine on the response to tyramine but did not modify the potentiation of the response to noradrenaline. Prolonged treatment with cocaine did not lower the tissue noradrenaline levels and did not prevent the noradrenaline depletion by reserpine. It is suggested that interactions between cocaine, tyramine and noradrenaline occur at the point where noradrenaline enters its tissue store.
MECHANISM WHEREBY HALOTHANE REVERSES THE PRESSOR RESPONSES TO ACETYLCHOLINE
Authors: GARDIER R. W. , RICHARDS A. B. , STOELTING V. K. , WHITE N.
Published: July 2012

The initial and secondary components of the biphasic pressor response to acetylcholine in the atropinized dog were analysed separately. Deep halothane anaesthesia reversed the initial pressor response to acetylcholine owing to a decrease in total peripheral vascular resistance in the absence of an increase in cardiac output. The secondary pressor response was not reversed but was suppressed owing to a marked reduction of the increase in cardiac output responsible for this pressor response; total peripheral resistance increased. Conversely, halothane anaesthesia did not block the increase in blood glucose concentration resulting from the injection of acetylcholine. Thus, the change induced by halothane in the secondary pressor phase was apparently a consequence of cardiac depression rather than of adrenal medullary blockade. Compound P‐286 (N‐diethylaminoethyl‐N‐isopentyl‐N‐di‐isopropylurea), which produces a change in the pressor response to acetylcholine similar to that induced by halothane, prevents the hyperglycaemia due to acetylcholine. In some experiments, deep halothane anaesthesia depressed the cardiac inotropic but not the chronotropic response to acetylcholine. Such selective blocking action is believed to have a bearing on production of arrhythmias.
THE INCREASE IN THE TOXICITY OF YOHIMBINE INDUCED BY IMIPRAMINE AND OTHER DRUGS IN MICE
Authors: QUINTON R. M.
Published: July 2012

In mice, yohimbine appears to accentuate the normal “alarm” reactions (alerting, flight) to external stimuli. Imipramine increases this effect and at the same time converts a non‐lethal dose of yohimbine into a lethal one. The effect of imipramine is greatly reduced by adrenalectomy or by treatment with reserpine, syrosingopine, ganglion‐blocking drugs or adrenaline antagonists acting on sympathetic β‐receptors. Hypnotic, anti‐convulsant or anaesthetic agents, tetrabenazine or antagonists of 5‐hydroxytryptamine do not reduce the imipramine effect. A variety of drugs which, like imipramine, are known to interfere with the tissue binding of noradrenaline also increase the toxicity of yohimbine. Yohimbine significantly reduces brain noradrenaline content; adrenal catechol amines are slightly reduced. The results suggest that yohimbine releases noradrenaline from stores or nerves as a consequence of increased central sympathetic activity. Imipramine increases the actions and toxicity of yohimbine by increasing the effects of the released noradrenaline on β‐receptors. The lethal effects of a high dose of yohimbine alone are not reduced by any of the treatments tested, and appear not to result from activation of sympathetic mechanisms.
BALANCED INCOMPLETE BLOCK DESIGNS IN BIOLOGICAL ASSAY ILLUSTRATED BY THE ASSAY OF GASTRIN USING A YOUDEN SQUARE
Authors: COLQUHOUN D.
Published: July 2012

General equations are given for computing the results of any (j+j) dose parallel line biological assay based on an incomplete block design. Only the information from comparisons within blocks is used. The computation is illustrated numerically by means of a (2+2) assay of gastrin devised and performed by Lai (1962), in which only three of the four doses could be given to each animal.
THE INTERACTION OF SOME STIMULANT AND DEPRESSANT DRUGS ON THE FROG HEART
Authors: BROADBENT J. L.
Published: July 2012

The activity of frog isolated hearts was depressed by altering the perfusing Ringer solution in five different ways: by reducing the calcium content, by increasing the potassium content, and by adding ether, thiopentone or acetylcholine. Depressed hearts were perfused with Ringer solution containing the following stimulant drugs: paullinia tannin, tannic acid, hydrogen peroxide, sodium oleate, sodium caprylate and ouabain. All these stimulant drugs had similar actions on hearts depressed by calcium lack, ether and thiopentone; hearts depressed by acetylcholine were, however, only weakly stimulated. Hearts depressed by potassium were readily stimulated by oleate, caprylate and paullinia tannin; ouabain and hydrogen peroxide had weak stimulant actions on hearts depressed by potassium, and tannic acid had a negative inotropic action. The differing actions on hearts depressed by potassium are probably related to differences in the degrees of fixation of the stimulant drugs. The mode of action of ouabain and the functional lesion in hearts depressed by narcotics are discussed.
TACHYPHYLAXIS TO SOME SYMPATHOMIMETIC AMINES IN RELATION TO MONOAMINE OXIDASE
Authors: DAY M. D. , RAND M. J.
Published: July 2012

Tachyphylaxis to the effects of indirectly acting sympathomimetic amines has been studied on the blood pressure of the cat, rabbit and rat, on the cat spleen and nictitating membrane and on the rabbit heart. The pressor responses to tyramine and to phenethylamine declined slowly with repeated injection; the extent of tachyphylaxis induced by these amines depended on the dosage and on the frequency of injection. The pressor responses to α‐methyltyramine and to dexamphetamine (α‐methylphenethylamine) declined rapidly with successive injections. The tachyphylaxis induced by one indirectly acting sympathomimetic amine is crossed to others, but not to directly acting amines, such as noradrenaline. In animals treated with nialamide, a drug which inhibits monoamine oxidase, the tachyphylaxis induced by tyramine and by phenethylamine was similar to that produced by their α‐methyl derivatives in normal animals. Similar results were obtained when the responses to indirectly acting sympathomimetic amines were studied on the cat spleen in situ and on the rabbit heart in vitro. Indirectly acting sympathomimetic amines impaired the responses of the cat nictitating membrane to sympathetic nerve stimulation; this effect was most evident with α‐methylated amines.
PREVENTION BY ANTAGONISTS OF THE TOXIC ACTION OF 5‐HYDROXYTRYPTAMINE ON PREGNANCY
Authors: POULSON EVELYN , ROBSON J. M.
Published: July 2012

As 5‐hydroxytryptamine can interrupt pregnancy in all its stages in mice and as pregnancy can be protected from the action of 5‐hydroxytryptamine by either progesterone or by prolactin only in early (days 1 to 6) but not in late pregnancy (day 14), the present experiments with two antagonists of 5‐hydroxytryptamine, namely methysergide and cyproheptadine, were carried out. Each compound antagonized the action of 5‐hydroxytryptamine in late pregnancy. The toxic effects produced by 5‐hydroxytryptamine are probably due to a direct action on the placental circulation which is prevented by the antagonists. In early pregnancy, methysergide prevented the effect of 5‐hydroxytryptamine, which is believed then to act on the central nervous system, interfering with luteal activity. Cyproheptadine alone interrupted early pregnancy, an action which was prevented by progesterone.
NOCICEPTIVE RESPONSES OF GUINEA‐PIGS TO INTRADERMAL INJECTIONS OF BRADYKININ AND KALUDIN‐10
Authors: COLLIER H. O. J. , LEE I. R.
Published: July 2012

Nine behavioural responses were observed to follow with reasonable frequency intradermal injection into guinea‐pigs of strongly anisotonic solutions, which are known to cause pain in human skin. These responses were recorded on a form, and a procedure was devised for obtaining a nociceptive score from the records. Intradermal injection of bradykinin or kallidin‐10 gave a response pattern indistinguishable from that to a strongly anisotonic solution. Each kinin raised the nociceptive score in response to the control solutions, as also did acetylcholine and histamine; but 5‐hydroxytryptamine and pH changes within the range of 3.1 to 10.3 did not significantly raise the control score. The effect of bradykinin was depressed by subcutaneous injection of morphine or codeine, but was unaffected by amidopyrine, calcium acetylsalicylate, chlorpromazine or phenylbutazone.
PLASMA VOLUME EXPANSION BY RAPID INFUSION OF A LOW MOLECULAR WEIGHT DEXTRAN
Authors: DAVIES J. W. L. , RICKETTS C R. , WILLIAMS B. N.
Published: July 2012

Large infusions of a 10% solution of dextran of molecular weight 40,000 were given to dogs during 3 min using a specially designed apparatus. The initial expansion of plasma volume was about twice the volume of solution injected. Plasma volume then fell rapidly (with a half life of about 2 hr), more rapidly than the fall in dextran concentration (half‐life of about 4.5 hr). Fluctuations in plasma volume and protein concentration were repeatedly observed during the return towards normal values. At 5 to 6 hr renal excretion accounted for 40% of the infused dextran, about 20% was intravascular and the remaining 40% was presumably extra vascular. No dextran was found in the cerebrospinal fluid.
ACTION OF OUABAIN ON THE GUINEA‐PIG ISOLATED UTERUS
Authors: SULLIVAN T. J.
Published: July 2012

Uterine activity in vitro was measured isometrically by integrating tension against time, and contractions were recorded on a kymograph using a servo‐recorder. Ouabain caused a persistent contraction both of the spontaneously contracting and of the electrically stimulated uterus, the response depending upon the presence of calcium. After ouabain had induced a contraction of the spontaneously active uterus, relaxation to the baseline after washing out the ouabain was succeeded by a period of inactivity. Since the uterus could respond as usual to stimulation during this period, ouabain appeared to be selectively depressing spontaneous contractions. High concentrations of progesterone suppressed uterine activity and the response to ouabain. Ouabain reduced the susceptibility of the uterus to depression by anoxia.
ANAPHYLACTOID OEDEMA PRODUCED IN RATS BY CERTAIN DEXTRINS
Authors: VEILLEUX R.
Published: July 2012

The author has previously shown the conditioning role of the anaphylactoid reaction in the calcification of the snout and paws of the rat after the injection of certain metallic compounds. The present experiments show that it is the dextrin fraction of these compounds which causes these anaphylactoid phenomena before the calcifying response. This fact deserves special attention since dextrin is frequently used in the preparation of certain drugs.
THE NATURE OF THE ANTIPERISTALTIC FACTOR FROM WHEAT GLUTEN
Authors: BISHOP HILARY , FRAZER A. C. , ROBINSON G. B. , SCHNEIDER R.
Published: July 2012

The ultrafiltrate of an aqueous extract of gluten depressed the peristaltic reflex of the rat isolated jejunum. Further purification increased the activity of the extract 200‐fold. Biochemical analysis showed that this purified gluten ultrafiltrate contained over 50% of adenosine. Comparative studies of the effects of adenosine and crude gluten ultrafiltrate were carried out on various biological preparations in vitro and in vivo. Both substances depressed all preparations that contained smooth or cardiac muscle, adenosine being 200‐ to 1,000‐times more active than gluten ultrafiltrate. Large doses of gluten ultrafiltrate were spasmogenic to guinea‐pig isolated intestine; this was not found with adenosine. Neither substance had any demonstrable effect on striated muscle or on neuromuscular transmission. Both substances were inactivated by incubation with mammalian small intestinal mucosa and with purified adenosine deaminase. Therefore there seems little doubt that gluten ultrafiltrate owes its antiperistaltic action to its adenosine content.
THE EFFECTS OF CHOLINE AND OTHER FACTORS ON THE RELEASE OF ACETYLCHOLINE FROM THE STIMULATED PERFUSED SUPERIOR CERVICAL GANGLION OF THE CAT
Authors: MATTHEWS E. K.
Published: July 2012

When the superior cervical ganglion of the cat was perfused with Locke solution, the amount of acetylcholine released into the perfusate decreased during successive periods of repetitive stimulation of the preganglionic nerve. Addition of choline to the perfusion fluid prevented this decrease. Choline also significantly increased (P>0.01) the initial output of acetylcholine. In contrast, variation of the physostigmine concentration or of the pCO2 and pH of the perfusion fluid had no statistically significant effect (P>0.05) upon the initial release of acetylcholine.
THE EFFECTS OF NEOSTIGMINE UPON GANGLION RESPONSES AFTER ADMINISTRATION OF BLOCKING DRUGS
Authors: FENNER PENELOPE A. , HILTON J. G.
Published: July 2012

The effects of block of autonomic ganglia by chlorisondamine and by hexa‐methonium, the administration of neostigmine and of atropine upon blood pressure, nervous transmission through the superior cervical ganglion, stimulation of autonomic ganglia by dimethylphenylpiperazinium, and the carotid occlusion reflex, have been studied in the dog anaesthetized with sodium pentobarbitone. The results of these studies have shown: (1) A ganglion blocking agent blocks synaptic transmission in the superior cervical ganglion at the same time as it lowers blood pressure. Neostigmine administered after ganglion‐block raises the blood pressure without much change in the response to stimulation of the preganglionic cervical sympathetic nerve. (2) If the effects of preganglionic nerve stimulation are recorded as a contraction of the nictitating membrane, a ganglion‐blocking agent also abolishes this response at the same time as it blocks the reflex rise in blood pressure produced by occlusion of both common carotid arteries. Neostigmine administered under these conditions does not affect the responses of the nictitating membrane, but restores the carotid occlusion reflex. This restoration of reflex activity is sensitive to atropine, as is the blood pressure rise. (3) At the same time that neostigmine restores the carotid occlusion reflex, there is no restoration of sensitivity of autonomic ganglia to chemical stimulation by dimethylphenylpiperazinium. In these animals atropine not only blocked the restored carotid occlusion reflex, but produced a further inhibition of the pressor response to dimethylphenylpiperazinium. It is concluded that neostigmine may raise blood pressure by partially restoring autonomic ganglionic transmission, but that total ganglionic function is not restored.
THE RESPONSE OF THE ISOLATED SKIN OF RATS TO DRUGS AND ELECTRICAL STIMULATION
Authors: HELLMANN K.
Published: July 2012

A new method of transmural stimulation (Hellmann, 1963b) has been used to examine the responses of the rat panniculus carnosus, a skeletal muscle which lines the skin. This preparation responded to drugs and to electrical excitation in the same way as other mammalian skeletal muscle preparations. The relaxation phase, when examined with fast recording systems, was complicated by what appeared to be the “tone” of the muscle.
THE EFFECT OF INTRA(CEREBRO)VENTRICULAR RESERPINE ON THE ACETYLCHOLINE CONTENT OF THE HEART, ILEUM AND HYPOTHALAMUS OF THE DOG
Authors: MALHOTRA C. L. , PRASAD K.
Published: July 2012

The effect of injection of reserpine into the cerebral ventricles on the acetylcholine contents of the sino‐atrial node, ileum and hypothalamus of the dog was studied in ten dogs. Another group of five dogs served as a control. The effect of intravenous administration of reserpine, in the same dose as given intracerebroventricularly, was also studied on the acetylcholine content of these tissues in five dogs. General sedation, bradycardia, miosis, salivation, emesis and purgation were looked for. Tissues were removed 1 hr after administration of reserpine for estimation of acetylcholine content, which was increased in all the tissues studied. The increase in the peripheral tissues was greater than in the hypothalamus. The increase in the acetylcholine content was not quantitatively related to the other effects of reserpine. The increase in the acetylcholine content of the sino‐atrial node and the ileum and also the peripheral effects observed on intracerebroventricular administration of reserpine can be attributed to its central action. With the same dose of reserpine given intravenously the acetylcholine content of the sino‐atrial node was significantly increased, while that of the hypothalamus and ileum was not.
OBSERVATIONS ON THE USE OF THE HEN AND RABBIT ISOLATED AURICLES FOR THE DETERMINATION OF INOTROPIC POTENCY
Authors: LOCK J. A.
Published: July 2012

The electrically driven, isolated auricles from the rabbit and the hen have been used to compare the inotropic potency of a bufodiene aglycone with ouabain. The results from the hen auricle permit conventional statistical treatment and show a good degree of reproducibility. Results of inotropic potencies and toxicity determinations on the two drugs are discussed.
THE EFFECT OF SOME NEW ANTIHISTAMINES ON THE ANAPHYLACTIC MICROSHOCK OF THE GUINEA‐PIG
Authors: HERXHEIMER H. , STRESEMANN E.
Published: July 2012

The dose/response curves for the protective effects of the new antihistamine compounds trimeprazine, 10‐(3‐diethylamino‐2‐methylpropyl)phenothiazine 1,1‐dioxide hydrochloride (oxomemazine hydrochloride), cyproheptadine, homochlorcyclizine and methotrimeprazine against the anaphylactic microshock of the guinea‐pig were similar to that of promethazine. The first three compounds, however, protected at lower doses than promethazine (5 to 10 μg/kg). The protective effect of cyproheptadine lasted longer than 24 hr.
QUANTITATIVE EVALUATION OF GUINEA‐PIG ANAPHYLAXIS IN VIVO
Authors: HICKS R. , LEACH G. D. H.
Published: July 2012

Two methods for recording bronchoconstrictor responses to antigen injected into sensitized guinea‐pigs have been used to show that the dose/response relationship is a normal pharmacological one characterized by a sigmoid curve. Studies of desensitization indicate that the progressive decrease in sensitivity to repeated administrations of the same dose of antigen follows an exponential pattern. It is suggested that this approach might form a basis for reliable quantitative investigations of anaphylactic phenomena.
PRESENCE OF KALLIKREIN IN THE γ‐GLOBULIN PERMEABILITY FACTOR OF GUINEA‐PIG SERUM
Authors: DAVIES G. E. , LOWE J. S.
Published: July 2012

γ‐Globulin fractions isolated from guinea‐pig serum by chromatography on diethyl‐aminoethyl cellulose exhibited all the properties of kallikrein. From a range of amino acid esters tested, only esters of arginine and lysine were hydrolysed; the esterase and capillary permeability‐increasing activities of different samples were correlated. Both esterase and permeability‐increasing activities could be increased by the addition of certain albumin‐rich fractions or of glass beads previously treated with guinea‐pig serum.
THE ORIGIN OF THE ACETYLCHOLINE RELEASED SPONTANEOUSLY FROM THE GUINEA‐PIG ISOLATED ILEUM
Authors: JOHNSON E. S.
Published: July 2012

When the guinea‐pig isolated ileum had been previously treated with the anti‐cholinesterase, NN‐diisopropylphosphodiamidic fluoride (mipafox), and attached to an isotonic lever loaded with 0.5 g, it released acetylcholine into Krebs solution gassed with a mixture of 95% oxygen and 5% carbon dioxide. The amount of acetylcholine spontaneously released depended on the duration of the rest period. Cocaine, procaine or cooling the preparation to 25° C greatly reduced this spontaneous output of acetylcholine, thus providing evidence in support of nervous origin of the ester. Reduction of the calcium ion content of the Krebs solution to one‐twentieth of its usual value or increase in the magnesium ion content four‐fold, changes which inhibit the release of acetylcholine from somatic motor nerve‐endings, inhibited the output of acetylcholine from the ileum. When all the calcium of Krebs solution had been replaced by strontium one‐third of the control output of acetylcholine was obtained, but the smooth muscle of the guinea‐pig ileum would not respond to drugs under these conditions. Strontium could thus partially substitute for calcium in nerves but not in muscle. Hemicholinium‐3 (100 μg/ml.) inhibited the spontaneous release of acetylcholine and 400 μg/ml. of choline was required to reverse the inhibition. It is concluded that cocaine, procaine, cooling, reduction of calcium ion and increase of magnesium ion concentrations all reduce the spontaneous output of acetylcholine, which has its origin in the parasympathetic nerve‐endings of the intramural nerve plexuses. Further, the hemicholinium experiments seem to justify the conclusion that the release of acetylcholine is reduced because synthesis is reduced.
OBSERVATIONS ON A VASOACTIVE MATERIAL IN BRAIN EXTRACTS
Authors: WHITE T.
Published: July 2012

The extraction and chromatographic purification of a vasoactive material in brain tissue are described. It is inactive on the guinea‐pig isolated ileum and rat uterus. Its chemical identity is as yet unknown. It is insoluble in nonpolar organic solvents, is stable in watery solution, but is inactivated by oxidizing agents. It is probably neither a nucleotide, a known amine, nor an inorganic salt.
THE RESPONSES OF THE GUINEA‐PIG ISOLATED INTACT TRACHEA TO TRANSMURAL STIMULATION AND THE RELEASE OF AN ACETYLCHOLINE‐LIKE SUBSTANCE UNDER CONDITIONS OF REST AND STIMULATION
Authors: CARLYLE R. F.
Published: July 2012

A preparation of the guinea‐pig isolated intact trachea is described which allows transmural stimulation of the intrinsic nerves of the tracheal muscle with simultaneous measurement of the volume changes of the trachea caused by contraction or relaxation of the tracheal muscle. The apparatus allows fluid to be removed from the lumen and outside of the trachea for assay of acetylcholine. The response to transmural stimulation over a range of 1 to 50 shocks/sec is first a contraction followed by a relaxation. The contraction is best seen at high frequencies of stimulation and is abolished by atropine. The contraction is enhanced by treatment of the trachea with the anticholinesterase NN‐diisopropylphosphodiamidic fluoride (mipafox), and is thus probably due to stimulation of intrinsic cholinergic nerves. The relaxation is maximal at low frequencies of stimulation. After treatment with mipafox a substance resembling acetylcholine is released in the absence of stimulation. The acetylcholine output rises following transmural stimulation, probably due to release of acetylcholine from cholinergic motor nerves. No relationship between frequency of transmural stimulation and release of acetylcholine has been seen in nine of ten experiments. The resting and stimulated release of acetylcholine is not greatly reduced by attempted separation of the tracheal muscle from the bulk of the trachea. This result suggests that acetylcholine outputs from the intact trachea are a measure of release from the smaller tracheal muscle.
PERIPHERAL VASCULAR EFFECTS OF MIXTURES OF ISOPRENALINE AND NORADRENALINE IN MAN
Authors: GLOVER W. E. , SHANKS R. G. , STANFORD C. F.
Published: July 2012

Mixtures of isoprenaline (0.05 μg/min) and noradrenaline (0.05, 0.1 and 0.25 μg/min) were infused into the brachial artery of subjects. The response, an initial transient increase in forearm blood flow followed by a decrease to or below the resting level, resembled the response to an intra‐arterial infusion of adrenaline (0.05 to 0.5 μg/min). A five‐fold increase in the dose of both drugs in the mixture resulted in a response which was matched by that to a five‐fold increase in the dose of adrenaline. The intra‐arterial infusions of mixtures and of adrenaline both reduced the thermal conductivity of the skin of the forearm. This result suggests that blood vessels in skeletal muscle responded qualitatively in the same manner to these infusions. Mixtures of isoprenaline (2 μg/min) and noradrenaline (10 μg/min) were infused intravenously into the subjects. The response was an initial transient increase followed by a smaller but sustained increase in the flow of blood to the forearm, and a fall in the flow of blood to the hand. These responses resembled those to the intravenous infusion of adrenaline (10 μg/min). We conclude that the action of adrenaline in the human arm can be explained on the basis of the response of two types of catechol amine receptor.
SECRETORY RESPONSES OF EXTRAMEDULLARY CHROMAFFIN TISSUE
Authors: MUSCHOLL E. , VOGT MARTHE
Published: July 2012

When the isolated inferior mesenteric ganglion of the dog was perfused with Locke solution, the effluent fluid contained noradrenaline and adrenaline. At rest the output of noradrenaline ranged from 0.7 to 40 ng/min, and that of adrenaline from 0.7 to 25 ng/min. Electrical stimulation of the inferior splanchnic nerves did not alter the catechol amine content of the perfusate, and stimulation of the ascending mesenteric nerves caused an increase to little more than twice the resting value. When acetylcholine or dimethylphenylpiperazinium iodide was infused into the preparation, the catechol amine content of the effluent fluid was 6‐ to 100‐times the resting level. Two drugs with muscarinic action (pilocarpine and 3‐acetoxy‐1‐benzyl‐1‐methylpyrrolidinium bromide) produced only very small increases in catechol amine release. Angiotensin, in doses ranging from 20 ng to 2 μg, inhibited release of catechol amines, and bradykinin had a weak stimulatory effect. It is suggested that the catechol amines released into the effluent fluid were derived from chromaffin tissue in the ganglion; evidence for innervation of this tissue was unobtainable, but its catechol amines were readily released by the injection of nicotinic drugs.
ANGIOTENSIN AND PERIPHERAL SYMPATHETIC NERVE ACTIVITY
Authors: BENELLI G. , BELLA D. DELLA , GANDINI A.
Published: July 2012

On the isolated vas deferens of the guinea‐pig angiotensin potentiated strongly the height of contractions due to electrical stimulation of the hypogastric nerve; it did not affect the responses to noradrenaline and acetylcholine, nor did it elicit any contraction when given alone. Angiotensin likewise potentiated the responses of the cat spleen to nerve stimulation, but it also induced by itself strong contractions of the organ and reduction of the venous outflow. In experiments on the arterial blood pressure of anaesthetized and spinal cats, in which sympathetic postganglionic transmission was temporarily blocked by nicotine or tetramethylammonium, pressor responses to angiotensin were strongly reduced. As with some ganglion‐stimulating drugs, the pressor responses, enhanced after a second series of nicotine injections, were reduced to the control level by hexamethonium. These findings indicate the involvement of peripheral sympathetic nerves in the action of angiotensin: the hypothesis is advanced that angiotensin acts at the peripheral nerve endings by promoting a greater output of noradrenaline.
KINETICS OF SERUM AMINOSALICYLIC ACID LEVELS
Authors: ENGBERG‐PEDERSEN H. , MØRCH P. , TYBRING L.
Published: July 2012

A mathematical model, involving three consecutive first order reactions, has been applied to already existing experimental material in order to explain the hourly variation in serum levels obtained after administration of varying repeated doses of different preparations of p‐aminosalicylic acid to human volunteers. The model closely agrees with the experimental data for all the orally administered preparations concerned, and the differences in blood levels for different preparations can be explained in terms of the values attributed to the parameters involved in the model. The same model adequately describes the elimination of aminosalicylic acid from the blood after a single intravenous infusion provided that the initial blood level attained does not exceed about 11 mg/100 ml., but fails at higher values. In the latter instance a second order model gives a good fit to the experimental curves. The increase in serum levels found experimentally for the same subjects during the first weeks of prolonged treatment with phenyl‐p‐aminosalicylate corresponds to a change in the values of the parameters for the elimination from the blood only.