Observations on 'fade': a complication of the contractile response of smooth muscle to a large dose of an agonist.
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1. A study has been made of the time course of contraction of guinea-pig isolated ileum when suddenly exposed to a high concentration of acetylcholine, carbachol or histamine. With a sufficiently large dose there was a ;fading' of the abrupt initial contraction. A sustained contraction followed, provided that the agonist was not washed out of the organ bath.2. The fade produced by giving large equipotent doses of acetylcholine and histamine simultaneously was substantially greater than that obtained by giving either agonist alone. It was comparable to that produced by a double dose of acetylcholine or histamine. This result does not support any explanation of fade based on receptor occupancy.3. The extent of fade and the level of the sustained contraction were strongly affected by the calcium concentration of the bath fluid: the higher the calcium concentration the less was the fade. It is suggested that fade occurs when there is such intense stimulation of receptors that excitation-contraction coupling becomes temporarily less efficient due to depletion of calcium from a store. (+info)
Studies on prostaglandin antagonists.
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1. Three prostaglandin antagonists have been examined for their ability to block PGE(2) and PGF(2alpha) on human, guinea-pig and isolated rat gastrointestinal muscle.2. 7-oxa-13-Prostynoic acid was either a non-selective antagonist, or was ineffective on the tissues studied; it had marked spasmogenic activity on the rat fundus.3. 1-Acetyl-2-(8-chloro-10,11-dihydrodibenz (b,f)(1,4) oxazepine-10-carbonyl) hydrazine selectively antagonized the excitatory effects of PGE(2) and PGF(2alpha) in guinea-pig and rat tissues, but not in human muscle.4. Polyphloretin phosphate selectively antagonized the excitatory effects of prostaglandins in both human and guinea-pig muscle preparations, but it caused stimulation of the rat fundus.5. All the antagonists lowered the tone in many tissues. They also reduced contractions caused by potassium.6. None of the compounds blocked the inhibitory effect of PGE(2) on intestinal circular muscle.7. The implication of these results on the nature of prostaglandin receptors, and the value of each compound as a prostaglandin antagonist are discussed. (+info)
Inhibitory effects of aprotinin on kallikrein and kininases in dog's blood.
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1. The blood-bathed organ technique was used in dogs to estimate kinin generation in the blood. Strips of cat jejunum were used as assay tissues.2. Infusions of kallikrein at 0.5-8 mU / ml into the blood in the extracorporeal circuit led to a generation of kinin at 0.6-10 ng / ml. The kinin generated was at the same concentration after incubation of kallikrein with blood for 15 s or 120 seconds. Intravenous infusions of kallikrein at (8-125 mU / kg) / min led to similar blood concentrations of kinin. These infusions induced substantial falls in blood pressure.3. Aprotinin inhibited the generation of kinin by kallikrein, but the concentration needed in vivo was 20,000 times higher than would be expected from the definition of the units.4. After intravenous injection of large doses of aprotinin, the kallikrein-inhibiting activity passed off within 40-60 minutes. At the same time, there was a gradual reduction in kininase activity, so that the half life of bradykinin in blood increased from a mean of 13 s to 40 seconds. This effect reached a maximum 1-3 h after injection of aprotinin.5. It is suggested that a metabolite of aprotinin is responsible for the kininase inhibition and that this effect may limit the usefulness of aprotinin in man. (+info)
The effect of age, species and adrenaline on the recovery of isolated atria from anoxia.
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1. The rate of recovery of the force of contraction of isolated atria from different species of mature animals after 1 hour of anoxia was recorded.2. Atria from rabbits of different ages were also exposed to anoxia. Atria from rabbits, ranging in age from 8 days to 3 years, were essentially similar in their recovery from anoxia, which was significantly slower than that of atria taken from rabbit foetuses at the 25th day of gestation.3. Atria from human foetuses at 12-16 weeks of gestation recovered from anoxia much faster and more completely than any other atria studied and it is postulated that this may be due, in part, to the concentration of endogenous catecholamines being low.4. The addition of propranolol to the organ bath had no effect on the recovery of atria from anoxia but prevented the action of added adrenaline, which manifests itself in a slowing of the rate and incompleteness of the recovery. (+info)
Long-lasting convulsant effect on the cerebral cortex of Naja naja venom.
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1. A neurotoxic fraction has been prepared from Indian cobra venom (Naja naja) by column chromatography on CM Sephadex.2. When assayed for lethality in mice, or for neuromuscular blocking potency in the rat phrenic nerve-diaphragm preparation, this fraction was 2.4-2.9 times as potent as whole venom.3. Application of either whole venom (0.5-1.0 mg/ml) or the neurotoxic fraction (0.25-1.0 mg/ml) to the exposed cerebral cortex of the rat led to the appearance in the somatosensory evoked potential of abnormal negative waves, resembling in amplitude and latency those produced by the cortical application of strychnine or curare.4. This effect differed from that produced by strychnine or curare in that after washing off the toxin the abnormal responses persisted for as long as the experiment continued (8-9 hours). (+info)
Inhibitory and excitatory effects of sympathomimetic amines on muscle strips from the stomach of the guinea-pig.
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1. Responses of muscle strips from the stomach of the guinea-pig have been recorded. Sympathomimetic amines cause inhibitory, motor or biphasic responses.2. The motor components of the responses of the preparations were greatly enhanced by the removal of the mucosal layers.3. The inhibitory responses to isoprenaline, noradrenaline and phenylephrine were antagonized by propranolol or by sotalol. The inhibitory responses to noradrenaline and phenylephrine but not isoprenaline were antagonized by phentolamine. Therefore, both alpha- and beta-adrenoceptors may subserve inhibition.4. The motor responses to noradrenaline and phenylephrine were often potentiated by propranolol or sotalol and were antagonized by phentolamine. Therefore, motor responses to sympathomimetic amines appear to involve alpha-adrenoceptors.5. The responses to sympathomimetic amines and their antagonists were not modified by hyoscine or by tetrodotoxin. It is concluded that the adrenoceptors mediating the responses recorded from these preparations are located on the smooth muscle cells rather than on a nervous pathway. (+info)
Effect of antidiuretic hormone on human small intestinal water and solute transport.
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The effect of i.v. Pitressin (ADH) in a dose of 1 U/hr on permeability characteristics and on absorptive capacity of the normal human small intestine was investigated. The method of continuous intestinal perfusion was employed with polyethylene glycol 4000 as a nonabsorbable marker. Unidirectional flux rates of Na and H(2)O were calculated from the disappearance of (22)Na and of (3)HOH from isotonic saline solution within the intestinal lumen. Each study consisted of two successive perfusion periods: one while the subject was hydrated, the other during ADH infusion or while the subject was dehydrated. Water and sodium absorption from isotonic NaCl occurred in the hydrated state and was abolished by ADH as well as by dehydration in the jejunum. In some instances, net gain of water and sodium in the lumen occurred. In the ileum, ADH and dehydration caused a decrease in water and sodium absorption rate. By contrast, unidirectional flux into the intestinal lumen of water and sodium, as well as dextrose and D-xylose diffusion, remained unchanged by ADH. During perfusions with hypertonic urea solutions the rates of sodium and water entry into the intestine were greatly increased during i.v. ADH infusion, whereas urea loss from the study segment remained constant. ADH in the dosage used did not affect human intestinal motility. The results suggest that circulating ADH in physiologic concentrations affects the small intestine in one of two ways: increased secretion of water and salt into the lumen or direct interference with the active sodium transport mechanism. (+info)
Timing of the auxin response in coleoptiles and its implications regarding auxin action.
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The timing of the auxin response was followed in oat and corn coleoptile tissue by a sensitive optical method in which the elongation of about a dozen coleoptile segments was recorded automatically. The response possesses a latent period of about 10 min at 23 degrees C, which is extended by low concentrations of KCN or by reducing the temperature, but is not extended by pretreatments with actinomycin D, puromycin, or cycloheximide at concentrations that partially inhibit the elongation response. Analysis of the data indicates that auxin probably does not act on the elongation of these tissues by promoting the synthesis of informational RNA or of enzymatic protein. Not excluded is the possibility that auxin acts at the translational level to induce synthesis of a structural protein, such as cell wall protein or membrane protein. While the data do not provide direct support for this hypothesis, the speed with which cycloheximide inhibits elongation suggests that continual protein synthesis may be important in the mechanism of cell wall expansion. (+info)