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[Increase in stability of isolated tissues and proteins caused by the action of chemical stimulants].

Chemical agents in subtoxic concentrations prolongate the survival time of living muscles and the time of contractile ability of glycerinated muscles. They preserve also the native property of actomyosine over the control time. The increase of resistance of living muscles and their models may be explained by stabilization of proteins or of their complexes. It is accompanied by the change of the indices of the functional state of the living muscle--by the decrease of the binding of vital dyes, by the hyperpolarization, by reducing the consumption of O2 and by the conservation of the quantity of SH groups at the high level.

Actomyosin

A modification of the dialytrode for simultaneous CNS recording and chemical stimulation.

Currently, chemical stimulation of the brain is done either with a single cannula that is inserted at the time the drug is delivered or with two cannulae that permit perfusion of the area of interest. The dialytrode is a push-pull cannula consisting of two concentric tubes, a porous membrane covering the tip of the tubing and a platinum wire loop that extends around the membrane and is used for EEG recordings. Studies with the dialytrode indicate that while the membrane is relatively impermeable to bacteria, molecules the size of neurotransmitters pass easily through the membrane. Therefore, the dailytrode is well suited for chronic chemical stimulation studies.

Amygdala

Chemical stimulation of single human fungiform taste papillae: sensitivity profiles and locus of stimulation.

Psychophysical responses to chemical stimulation of single human fungiform taste papillae were obtained from 40 papillae in four subjects. Effects of solution concentration and locus of stimulation were examined for nine test compounds. Sensitivity profiles constructed for individual papillae showed that single fungiform papillae mediate more than a single taste quality. In addition, the chemical sensitivities of individual papillae were reflected in their thresholds for all compounds, and correlation coefficients between recognition thresholds were no greater for similar than for dissimilar tasting compounds. No differences in mediation of quality were found as a function of locus of stimulation on the papilla, although sensitivity was found to be greater on the dorsal surface than on the sides. The data were discussed within the context of previous studies of response characteristics of single papilla.

Adolescent

Effects of chemical stimulation of the mesolimbic dopamine system upon locomotor activity.

The effects of local injections of drugs into terminal areas of the mesolimbic dopamine system were investigated. Bilateral administration of dopamine, but not of noradrenaline and serotonin, into the nucleus accumbens of non-pretreated rats resulted in stimulation of locomotor activity. No clear or only minor effects were seen after injections of the dopamine metabolites 3-methoxytyramine, DOPAC and HVA and after injections of media with different pH and osmolality. d-Amphetamine proved more effective than dopamine in producing locomotor stimulation, whereas both stimulant and depressant effects were observed following injection of apomorphine into the nucleus accumbens. ET 495 and the noradrenaline agonists clonidine, phenylephrine and isoprenaline did not enhance locomotor activity, but theophylline was effective. Pretreatment with haloperidol, but not with clozapine, significantly reduced the effects of dopamine and theophylline. Locomotor stimulation was also found following bilateral administration of dopamine, d-amphetamine and apomorphine into the tuberculum olfactorium, whereas noradrenaline, serotonin and ET 495 produced no, or rather depressant effects. These results provide further evidence for an important role of the mesolimbic dopamine system with respect to locomotor activity.

Animals

Properties of excitable sites in the squid axon membrane as revealed by use of chemical stimulants and a spectrum analyzer.

Properties of the excitable sites in the squid axon membrane were studied by using various chemical stimulants and a real-time spectrum analyzer. Intact squid axons immersed in media with a reduced divalent cation concentration develop very small electric responses (1-30 micronV in amplitude) which repeat at more-or-less regular intervals. The frequency of repetition of these miniature responses falls when the temperature of the axon is lowered. Replacement of a small fraction of the external Na-ion with K-ion is a powerful means of generating miniature responses. Passage of an outwardly directed current through the axonal membrane also evokes miniature responses. This effect of an electric current is attributed to a transport of intracellular K-ion into the axonal membrane. The results of the effects of external application of the salts of Li-, Rb- and Cs-ion indicate that the ability of alkali metal ions to induce miniature response falls in the following order: K, Rb is greater than Cs is greater than Na is greater than Li.

Animals

[Collected findings of long-lasting chemical stimulation of the immune system by N-(2-cyanethylene)-urea derivatives (author's transl)].

The present paper describes our findings so far on the long-lasting chemical stimulation of the immune system by means of various batches from the synthesis of N-(2-cyanethylene)-urea (BA 1). These findings were also supported by results of other authors. Furthermore some recent findings have demonstrated that 2-cyanaziridine, 2-cyanethyl-urea and a bicyclic isomer represent examples for immunologically effective BA 1-derivatives or BA 1-isomers, respectively.

Animals

Chemical stimulation of Schistosoma mansoni miracidial activity.

The movements of S. mansoni miracidia immersed in various solutions of organic chemicals were recorded by dark ground photography. Reduction of miracidial speed was recorded for miracidia in solutions of fatty acids and ammonia. The speed reduction was concentration dependant and pH dependant, indicating in both cases that the un-ionized molecule was responsible. Ammonia at concentrations between 0.4 mM and 0.8 mM elicited an increased "rate of change of direction" by miracidia. No changes in miracidial movements were recorded for miracidia immersed in aqueous solutions of amino acids, sugars or of molluscan nitrogenous excretion products other than ammonia. A possible role for chemo-klinokinetic behaviour patterns in miracidial host location was formulated.

Amino Acids

Effects of mechanical and chemical stimulation of fine muscle afferents upon primate spinothalamic tract cells.

1. Injections of algesic chemicals were made into the arterial circulation of the triceps surae muscles in anaesthetized monkeys. 2. The responses of a sample of primary muscle afferents suggest that what is known about the activation of muscle afferents in the cat by algesic agents applies also to the monkey. One exception to this is the activation of many group I afferents by KCl in the monkey, but not in the cat. 3. Many spinothalamic tract cells were powerfully excited by the intra-arterial injection of algesic chemicals (bradykinin, 5-hydroxytryptamine (5-HT), KCl) in preparations in which the hind limb was denervated except for the nerves to the triceps surae muscles. The excitatory action of bradykinin had a slower time course than did that of 5-HT or KCl. 4. A number of the spinothalamic tract cells which failed to respond to chemical activation of muscle afferents were located in lamina I of the spinal cord. 5. Repeated injections of bradykinin produced similar responses, whereas the effects of 5-HT injections showed marked tachyphylaxis. 6. No evidence was obtained that activation of muscle spindle afferents by succinylcholine injections resulted in the excitation of spinothalamic tract neurones in the population sampled. 7. Injections of hypertonic NaCl into muscle or tendon produced a prolonged excitation of many spinothalamic tract cells. 8. It is concluded that a substantial proportion of primate spinothalamic tract cells receive a convergent input from cutaneous and muscle receptors. The muscle receptors involved appear to include primary afferents of group III and IV calibre. The possibility is suggested that such cells could play a role in the production of poorly localized pain.

Animals

New multi-purpose chemitrodes for electrical and chemical stimulation or localized perfusion of the brain.

The design and construction of two sizes of bipolar chemitrodes are described for stimulating directly a single site in the brain of a rat, cat, monkey or other animal. These chemitrodes are used for the injection of a drug at the same time that electrical stimulation is applied, or for the localized push-pull perfusion of the same locus. They also permit the recording of electrical potentials at the tip of the guide tube. The chemitrodes may be implanted chronically for the purpose of examining the relationship between chemically and electrically elicited responses in the awake and unrestrained animal.

Animals

Descending influences on the responses of spinocervical tract neurones to chemical stimulation of fine muscle afferents.

1. In cats, extracellular micro-electrode recordings were made from axons of the spinocervical tract (s.c.t.) in both the decerebrate state and during cold block of the spinal cord (reversible spinal state) to examine the effects of intra-arterial injection of algesic agents (bradykinin, potassium, 5-hydroxytryptamine) into the gastrocnemius-soleus (g.s.) muscle on the discharge behaviour of s.c.t. neurones.2. In the decerebrate state without cooling the spinal cord 13% of the cells (eleven out of eighty-three) responded to intra-arterial injection of bradykinin, 33% (twenty-two out of sixty-nine) to 5-hydroxytryptamine, and 38% (thirty-five out of ninety-one) to potassium injection.3. The general time course and the latency of the responses of s.c.t. cells induced by injection of pain-producing substances into the g.s. muscle reflect in many respects the activations of g.s. group III and group IV primary afferent units studied previously.4. For twenty-seven s.c.t. neurones the period of recording was long enough to record the responses of the same cell to injections of algesic agents in both the decerebrate and the reversible spinal state. In the reversible spinal state 83% (nineteen out of twenty-three) of the s.c.t. neurones tested with all the three substances responded to at least one of the algesic agents. In the decerebrate state the percentage was lower (39%).5. Reversible spinalization led not only to a significant increase in the number of s.c.t. neurones responding to the algesic agents used but also to an increase in the magnitude of the chemically induced responses.6. The mean latency of the responses of neurones that were activated in both preparations were shorter in the reversible spinal state than in the decerebrate state.7. Control experiments showed that the responses to bradykinin and potassium were entirely due to the nervous outflow from the g.s. muscle. In contrast, intra-arterially applied 5-hydroxytryptamine influenced the s.c.t. cells via unknown additional sites of action.8. The results indicate that muscular group III and/or group IV units excitable by algesic substances do project on to neurones of the spinocervical tract. Furthermore it is concluded that the responses of s.c.t. neurones to activation of fine muscle afferents by algesic agents are subject to a descending control similar to the well known descending modulation of their responsiveness to cutaneous input. Therefore, in addition to serving as a cutaneous pathway the spinocervical tract may take part in muscular nociception.

Action Potentials

Responses of group IV afferent units from skeletal muscle to stretch, contraction and chemical stimulation.

In an attempt to differentiate between nociceptive group IV muscle receptors and "ergoceptive" ones, the discharges of single group IV fibres from skeletal muscle in response to local pressure, sustained stretch, repetitive contraction and intra-arterial injections of bradykinin, 5-hydroxytryptamine (5-HT), potasssium, phosphate, and lactate were studied in anesthetized cats.

Animals