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503 Influence of narcotic drugs upon the reactiveness of skeletal muscles to acetylcholine and potassium ions
151
Abstracts of Papers The progressive fall in the potential of the motor plate was, however, noted, showing that the action is either at the lrvrl of the plate or on the nerve fibre or its endings. (3) the toxin exerts a direct inhibitory effect on muscle fibre, as direct electrica: stimulation of an innervated or denervated muscle fibre no longer produces contraction after the effect of the toxin. (4) the conduction of the nerve inflow is blocked in the frog sciatic-gastrocnemius preparation; weak concentrations of the toxin block the conduction of motor nerve inflow and this effect may explain the drop in potential at the motor plate. (5) in iitro. acetylcholine does not form an inactive complex with the toxin. (6) does it prevent biosynthesis or liberation of the Experiphysiological transmitter of motor inflow? mental results (increased amplitude of contractions with rise in frequency, reduced sensitivity of a nerve muscle preparation in situ near to the injection of acctylcholine) furnish indirect proof providing little support for such a mechanism. Summary: Tetrodotoxin has a complex and atypical action bringing into play at least two phenomena: direct inhibition of the muscle fibre and blocking of the conduction of motor nerve inflow.
501 Effect of Adrenaline and Noradrenaline on Tension Developed in Cat’s Soleus and Tibia& Anterior Muscles Stimulated at Various Frequencies. I. JURNA and 11’. RUSIMEL (Germany). In cats anaesthctized with nembutal, soleus and tibialis anterior muscles were isolated. The peripheral ends of the dissected motor nerves were stimulated at 10, 15, 20, 30 and 40 (50) stimuli per set (suband supramaximal shocks). Various amounts of extension were applied to the muscles previous to stimulation. Tension was recorded isometrically. In tension-frequency diagrams the tension of the soleus muscle followed an exponential curve, which was steepest and nearly linear from A plateau was reached at 40 or 10 to 20 per sec. 50 per see. With tibialis anterior no plateau was reached up to the maximal frequencies tested; tension increase with stimulation frequency was largest within the range from 20 to 30 or 40 per sec. Adrenaline and noradrenaline caused a reduction of muscle tension in soleus and an increase in tibialis anterior, as has been previously reported With supramaximal stimuby Bowman et al.“’ lation, the decrease of tension in the soleus muscle injection of adrenaline following intravenous (0.5-1.0 pg/kg) or noradrenaline (1.0 yg/kg) was most pronounced at lower frequencies (lo-20 per set) ; at higher frequencies both amines had little or no effect. With submaximal strength the decrease In tibialis in tension was seen at all frequencies. anterior adrenaline and noradrenaline (3.0-5.0 pg/
kg) caused
the largest
increase
in tension
at 20 and/
or 30 per sec. 1. BOWMAN and ZAIVIS (1958),
J.
Physiol., 144, 92.
502 The
Influence of Various Pharmacological Agents on the Rate of Rigor Mortis in V. R/I. KARASIK (U.S.S.R.). Skeletal Muscles.
The report is a review of works, performed by the author and his collaborators (I. V. Markova, E. \-. Moreva, A. I. Podesnaya, L. I. Tank). A method to register the rate of development of rigor of the tail in mice and rats, was elaborated. After administration of the drug decapitation (stopping the oxidative phosphorylation whereas the glycolytic phosphorylation lasts for a some time) was carried out and time of rigor wan determined. The rigor is distinctly accelerated after 2 :4dinitrophenol (DNP), less distinctly after sodium azide and least of all after fluoride, monoiodacetate and iodacetamide (all substances in sublethal doses). After sublethal doses of DNP, the rigor apprarcd when the ATP content in muscles was relatively high. It is possible that DNP disturbs such transphosphorylation process, which maintains the native state of contractile protein. Injection of epinephrine, which promotes the phosphorylation, restores the time of rigor, accclerated by DNP, but it does not influence the time of rigor in normal animals. The rigor is retarded after injection of insulin, promoting the glucokinase reaction, and after adrenalectomy, when the inhibitory influence of glucocorticoids on the glucokinase reaction was abolished. The injection of the adrenal cortex preparation “Cortin” (but not cortisone or DOCA) in adrenalectomized animals restores the time of rigor. The rigor in newborn mice, rats, rabbits and cats) (but not in guinea pigs) appeared later than in The latter must be connected with adult animals. failure of glucocorticoids secretion in the newborn and probably with a longer native state of contractile protein.
503 Influence of Narcotic Drugs upon the Reactiveness of Skeletal Muscles to AcetylE. V. MOREVA choline and Potassium Ions. (U.S.S.R.). Narcotic drugs reduce or even abolish contracture of the m. rectus abdominis of the frog brought about by potassium. 4t the same time they not only do not reduce acetylcholine contractures, but, in many cases, even intensify them. Analogous results are obtained in experiments on the isolated diaphragm of the rat. The author assumes the presence of some structural component in the skeletal muscle which is depressed by narcotic drugs and possesses a more
152 pronotmced acetylcholine.
selective
reaction
to potassium
than
to
Intensification of acetylcholine induced contracture under the action of narcotic drugs cannot be ascribed to cholinesterase depression, as has been shown in a former investigation,
504 Effect of Enzymes on Isolated Rat Mast CelIs. R. KELLER (Switzerland). The effect of a number of enzymes on mast cells isolated from the peritoneal cavity of the rat was investigated by phase contrast microscopy at 37°C as welt as by quantitative determination of the percentage of damaged cells after incubation of normal cells for 4 min at 37°C. The results of these investigations are in good agreement with those obtained on isolated rat mescnteries. Thus they confirm the observations of HSgberg.4” The significance of these findings is briefly discussed.
506 Uptake and Metabolism of Amines by Mast Cells in Culture. J. P. GREEN and S. X31. DAY (U.S.A.). Two strains of a murine mast cell tumour (P-81 5), maintained in culture for more than 2 years, retain the capacity to take up and to decarboxylate histidine and 5.hydroxytryptophan (.!I-HTP) to their respective amines. The ceils are able also to concentrate pre-formed histamine and .$hydroxytryptamine (5-HT). The rates of turnover of rxogenous histamine differs from the turnover-rate of endogenously formed histamine. Roth strains of nroplastic mast cells are able to take up 3-hydroxytyramine and tryptaminc, although to a lesser extent than histamine or 5-HT, but no evidence could be obtained that either 3-hydronytyramine or tryptamine are normally present in these cells. Incubation of these cells with tryptophan results in the formation of j-HTP and 5-HT and only smaif amounts of 5-hydroxyindole acetic acid; no other metabolic products of tryptophan or of 5-HT could be detected. No evidence could be obtained that either endogenous or exogenous histamine is further metabolized.
41, 345. 507 Response
before 505 Proteolytic
Enzyme and Tissue Activator Associated with Canine Mast Cell Tumour. N. ENDEand J. V. AUDITORE (U.S.A.).
In the past few years, the mast cell has been shown to be a veritable pharmacological storehouse. Recently the authors reported that the mast cell of the dcg and human is associated with an unidentified proteolytic enzyme. Preliminary studies on the intracellular distribution of this proteolytic enzyme revealed its presence in all compartments of the cell with greatest quantities in the mitochondrial fraction. Recent studies”’ have shown that 64 per cent of the total heparin is also present Tissue activator of in the mitochondrial fraction. the fibrinolytic enzyme system was also found associThe microsomal ated with the mast cell tumour. fraction contained most of this activity. Additional studies on the hydrolysis ofamino acid esters employing the Warburg technique show that the dog mast cell turnour hydrolyzes p-toluenesulphony1 arginine methyl ester (TAME) at an appreciable rate (7.2 $ CO,jlO min /Cl,3 ml homoFive other differmt types of genate) at pH 7.4. dog tumours failed to hydrolyze TrU4E tested in a similar system. Dog mast cell tumour homogenate was also found to hydrolyze acetyl-r.-tryptophan ethyl ester. The hydrolysis of this ester, however, was not believed to be a specific action of the homogenate of mast cells as different types of dog turnours also hydrolyzed this same amino acid ester. ___-1. KORN (1959),
3. Bid.Chem.
J.
to Histamine in Mental Patients and after Tranquilizer Therapy.
LEBLANC (Canada).
The skin of mental patients was shown to contain fewer mast cells than normally. However, after one month’s tranquilizer therapy the number of these cells increased significantly. The cutaneous response to histamine and tubocurarine was much smaller in mental patients than in normal subjects. However, patients who were sufficiently improved to be released after one month’s tranquilizer therapy, were more sensitive to histamine at the end of this period than they were originally. Unimproved patients showed no such increase in histamine response although after six month’s therapy they were shown to be less tolerant to histamine. Schizophrenics as a group showed a better response to tranquilizers, as judged by histamine sensitivity, than any other group of mental patients studied. 508 The Action of Adrenal Cortical Hormones on Histamine Metabolism. J. M. TELFORD and G. B. WEST (United Kingdom). Injections ofglucocorticoids reduce the histamine and 5-hydroxytryptamine contents of rat skin and small intestine but increase the levels of these amincs in the pyloric stomach.“’ Experiments have been carried out to determine if these changes are due to alterations in the rate of formation of the amines. The histidine decarboxylase activity of rat tissues was estimated using a modification of Waton’s method’*); with this technique, the most potent sources of the enzyme are the liver and pyloric stomach.‘31 Treatment with glucocorticoids in-
Abstracts of Papers The progressive fall in the potential of the motor plate was, however, noted, showing that the action is either at the lrvrl of the plate or on the nerve fibre or its endings. (3) the toxin exerts a direct inhibitory effect on muscle fibre, as direct electrica: stimulation of an innervated or denervated muscle fibre no longer produces contraction after the effect of the toxin. (4) the conduction of the nerve inflow is blocked in the frog sciatic-gastrocnemius preparation; weak concentrations of the toxin block the conduction of motor nerve inflow and this effect may explain the drop in potential at the motor plate. (5) in iitro. acetylcholine does not form an inactive complex with the toxin. (6) does it prevent biosynthesis or liberation of the Experiphysiological transmitter of motor inflow? mental results (increased amplitude of contractions with rise in frequency, reduced sensitivity of a nerve muscle preparation in situ near to the injection of acctylcholine) furnish indirect proof providing little support for such a mechanism. Summary: Tetrodotoxin has a complex and atypical action bringing into play at least two phenomena: direct inhibition of the muscle fibre and blocking of the conduction of motor nerve inflow.
501 Effect of Adrenaline and Noradrenaline on Tension Developed in Cat’s Soleus and Tibia& Anterior Muscles Stimulated at Various Frequencies. I. JURNA and 11’. RUSIMEL (Germany). In cats anaesthctized with nembutal, soleus and tibialis anterior muscles were isolated. The peripheral ends of the dissected motor nerves were stimulated at 10, 15, 20, 30 and 40 (50) stimuli per set (suband supramaximal shocks). Various amounts of extension were applied to the muscles previous to stimulation. Tension was recorded isometrically. In tension-frequency diagrams the tension of the soleus muscle followed an exponential curve, which was steepest and nearly linear from A plateau was reached at 40 or 10 to 20 per sec. 50 per see. With tibialis anterior no plateau was reached up to the maximal frequencies tested; tension increase with stimulation frequency was largest within the range from 20 to 30 or 40 per sec. Adrenaline and noradrenaline caused a reduction of muscle tension in soleus and an increase in tibialis anterior, as has been previously reported With supramaximal stimuby Bowman et al.“’ lation, the decrease of tension in the soleus muscle injection of adrenaline following intravenous (0.5-1.0 pg/kg) or noradrenaline (1.0 yg/kg) was most pronounced at lower frequencies (lo-20 per set) ; at higher frequencies both amines had little or no effect. With submaximal strength the decrease In tibialis in tension was seen at all frequencies. anterior adrenaline and noradrenaline (3.0-5.0 pg/
kg) caused
the largest
increase
in tension
at 20 and/
or 30 per sec. 1. BOWMAN and ZAIVIS (1958),
J.
Physiol., 144, 92.
502 The
Influence of Various Pharmacological Agents on the Rate of Rigor Mortis in V. R/I. KARASIK (U.S.S.R.). Skeletal Muscles.
The report is a review of works, performed by the author and his collaborators (I. V. Markova, E. \-. Moreva, A. I. Podesnaya, L. I. Tank). A method to register the rate of development of rigor of the tail in mice and rats, was elaborated. After administration of the drug decapitation (stopping the oxidative phosphorylation whereas the glycolytic phosphorylation lasts for a some time) was carried out and time of rigor wan determined. The rigor is distinctly accelerated after 2 :4dinitrophenol (DNP), less distinctly after sodium azide and least of all after fluoride, monoiodacetate and iodacetamide (all substances in sublethal doses). After sublethal doses of DNP, the rigor apprarcd when the ATP content in muscles was relatively high. It is possible that DNP disturbs such transphosphorylation process, which maintains the native state of contractile protein. Injection of epinephrine, which promotes the phosphorylation, restores the time of rigor, accclerated by DNP, but it does not influence the time of rigor in normal animals. The rigor is retarded after injection of insulin, promoting the glucokinase reaction, and after adrenalectomy, when the inhibitory influence of glucocorticoids on the glucokinase reaction was abolished. The injection of the adrenal cortex preparation “Cortin” (but not cortisone or DOCA) in adrenalectomized animals restores the time of rigor. The rigor in newborn mice, rats, rabbits and cats) (but not in guinea pigs) appeared later than in The latter must be connected with adult animals. failure of glucocorticoids secretion in the newborn and probably with a longer native state of contractile protein.
503 Influence of Narcotic Drugs upon the Reactiveness of Skeletal Muscles to AcetylE. V. MOREVA choline and Potassium Ions. (U.S.S.R.). Narcotic drugs reduce or even abolish contracture of the m. rectus abdominis of the frog brought about by potassium. 4t the same time they not only do not reduce acetylcholine contractures, but, in many cases, even intensify them. Analogous results are obtained in experiments on the isolated diaphragm of the rat. The author assumes the presence of some structural component in the skeletal muscle which is depressed by narcotic drugs and possesses a more
152 pronotmced acetylcholine.
selective
reaction
to potassium
than
to
Intensification of acetylcholine induced contracture under the action of narcotic drugs cannot be ascribed to cholinesterase depression, as has been shown in a former investigation,
504 Effect of Enzymes on Isolated Rat Mast CelIs. R. KELLER (Switzerland). The effect of a number of enzymes on mast cells isolated from the peritoneal cavity of the rat was investigated by phase contrast microscopy at 37°C as welt as by quantitative determination of the percentage of damaged cells after incubation of normal cells for 4 min at 37°C. The results of these investigations are in good agreement with those obtained on isolated rat mescnteries. Thus they confirm the observations of HSgberg.4” The significance of these findings is briefly discussed.
506 Uptake and Metabolism of Amines by Mast Cells in Culture. J. P. GREEN and S. X31. DAY (U.S.A.). Two strains of a murine mast cell tumour (P-81 5), maintained in culture for more than 2 years, retain the capacity to take up and to decarboxylate histidine and 5.hydroxytryptophan (.!I-HTP) to their respective amines. The ceils are able also to concentrate pre-formed histamine and .$hydroxytryptamine (5-HT). The rates of turnover of rxogenous histamine differs from the turnover-rate of endogenously formed histamine. Roth strains of nroplastic mast cells are able to take up 3-hydroxytyramine and tryptaminc, although to a lesser extent than histamine or 5-HT, but no evidence could be obtained that either 3-hydronytyramine or tryptamine are normally present in these cells. Incubation of these cells with tryptophan results in the formation of j-HTP and 5-HT and only smaif amounts of 5-hydroxyindole acetic acid; no other metabolic products of tryptophan or of 5-HT could be detected. No evidence could be obtained that either endogenous or exogenous histamine is further metabolized.
41, 345. 507 Response
before 505 Proteolytic
Enzyme and Tissue Activator Associated with Canine Mast Cell Tumour. N. ENDEand J. V. AUDITORE (U.S.A.).
In the past few years, the mast cell has been shown to be a veritable pharmacological storehouse. Recently the authors reported that the mast cell of the dcg and human is associated with an unidentified proteolytic enzyme. Preliminary studies on the intracellular distribution of this proteolytic enzyme revealed its presence in all compartments of the cell with greatest quantities in the mitochondrial fraction. Recent studies”’ have shown that 64 per cent of the total heparin is also present Tissue activator of in the mitochondrial fraction. the fibrinolytic enzyme system was also found associThe microsomal ated with the mast cell tumour. fraction contained most of this activity. Additional studies on the hydrolysis ofamino acid esters employing the Warburg technique show that the dog mast cell turnour hydrolyzes p-toluenesulphony1 arginine methyl ester (TAME) at an appreciable rate (7.2 $ CO,jlO min /Cl,3 ml homoFive other differmt types of genate) at pH 7.4. dog tumours failed to hydrolyze TrU4E tested in a similar system. Dog mast cell tumour homogenate was also found to hydrolyze acetyl-r.-tryptophan ethyl ester. The hydrolysis of this ester, however, was not believed to be a specific action of the homogenate of mast cells as different types of dog turnours also hydrolyzed this same amino acid ester. ___-1. KORN (1959),
3. Bid.Chem.
J.
to Histamine in Mental Patients and after Tranquilizer Therapy.
LEBLANC (Canada).
The skin of mental patients was shown to contain fewer mast cells than normally. However, after one month’s tranquilizer therapy the number of these cells increased significantly. The cutaneous response to histamine and tubocurarine was much smaller in mental patients than in normal subjects. However, patients who were sufficiently improved to be released after one month’s tranquilizer therapy, were more sensitive to histamine at the end of this period than they were originally. Unimproved patients showed no such increase in histamine response although after six month’s therapy they were shown to be less tolerant to histamine. Schizophrenics as a group showed a better response to tranquilizers, as judged by histamine sensitivity, than any other group of mental patients studied. 508 The Action of Adrenal Cortical Hormones on Histamine Metabolism. J. M. TELFORD and G. B. WEST (United Kingdom). Injections ofglucocorticoids reduce the histamine and 5-hydroxytryptamine contents of rat skin and small intestine but increase the levels of these amincs in the pyloric stomach.“’ Experiments have been carried out to determine if these changes are due to alterations in the rate of formation of the amines. The histidine decarboxylase activity of rat tissues was estimated using a modification of Waton’s method’*); with this technique, the most potent sources of the enzyme are the liver and pyloric stomach.‘31 Treatment with glucocorticoids in-