The localization of acetylcholinesterase in the locus coeruleus of the normal rat and after 6-hydroxydopamine treatment.
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The locus coerulus is a densely packed group of neurons in the floor of the fourth ventricle, and is the largest aggregate of noradrenaline-containing cells in the mammalian brain. The distribution within the locus of acetylcholinesterase (AChE), which is present in high concentration, has been studied at light and electron microscope level, both in normal rats and in ones treated with 6-hydroxydopamine. Neuronal enzyme activity is entirely intracellular and mainly concentrated in stacks of ER which occupy much of the cell cytoplasm. There are no indications of a cholinergic input. After 6-hydroxydopamine treatment extensive cell death occurs and AChE activity virtually disappears. A majority of the many blood vessels in the locus also stain strongly for AChE, unlike those present in most other areas of the rat brain. The locus coeruleus therefore represents an area of the rat brain with a high content of AChE, but no evidence of a cholinergic mechanism. Some possible explanations for this anomalous presence of AChE are briefly discussed. (+info)
Studies on the mechanism of shock. The importance of central catecholaminergic neurons in the response to injury.
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Destruction of central catecholaminergic nerve terminals and axons by the injection of 6-hydroxydopamine (6-OHDA) into a lateral cerebral ventricle lowered the resistance of rats to 4-h bilateral hindlimb ischaemia. Although treatment with 6-OHDA alters food intake and growth rate its effect on the resistance of rats to this injury could not be attributed to differences in the size of the limbs which were made ischaemic or in nutritional state. It was not seen after peripheral chemical sympathectomy produced by the intravenous injection of 6-OHDA. Pretreatment with intraventricular 6-OHDA affected the core temperature changes during and after the limb ischaemia and impaired the blood pressure response after removal of the tourniquets. The lesions in the hypothalamus associated with these changes were examined with fluorescence histochemistry and found to be severe and widespread. It was concluded that the catecholaminergic fibres innervating the hypothalamus and other parts of the brain concerned in homoeostasis play a beneficial role in the defence against injury. (+info)
Potassium-induced increase in oxygen consumption of brown adipose tissue from the rat.
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1. In brown adipose tissue, noradrenaline induces an increase in respiration and a depolarization of the cells. The effect of an increase in potassium concentration in a range known to depolarize the brown adipocytes was tested on the O2 consumption. 2. Isolated interscapular brown adipose tissue from the rat was incubated in chambers that allowed O2 consumption to be measured over prolonged periods. 3. 45-50 mM-KC1 were found to induce a more that fourfold increase in O2 consumption, which was stable, reversible and dependent upon the presence of calcium in the meduim. 4. When rats were pre-treated with reserpine or 6-hydroxydopamine the KC1-induced increase in O2 consumption was sharply reduced or entirely adsent. 5. The effect of KC1 was greatly inhibited by (-)-propranolol, but not by (+)-propranolol. 6. Moderate increases in O2 consumption induced by low concentrations of potassium were potentiated by desipramine, a drug which is known to block the uptake of catecholamines by adrenergic nerve endings. 7. Surgical denervation caused a decrease in the catecholamine content of the tissue, but had no effect on the KC1 response. 8. It is concluded that in brown adipose tissue, potassium stimulates O2 consumption by causing a release of noradrenaline from nerve endings. This implies that surgical denervation as it is commonly performed on this tissue does not denervate the brown adipocytes but probably only the blood vessels. (+info)
The modification of inotropic action of ouabain by 6-hydroxydopamine and alpha-methyl-p-tyrosine in dogs.
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The action of ouabain on myocardial inotropism pretreated with 6-hydroxydopamine and alpha-methyl-p-tyrosine was studied. Inotropic action of ouabain was not changed by depletion of catecholamines in the brain, in which the central sympathetic neurons were destroyed by an intraventricular administration of 6-hydroxydopamine. Systemic administration of 6-hydroxydopamine and alpha-methyl-p-tyrosine reduced ventricular catecholamines to 5.3% and 20.8% of the control, respectively. Percent increase of contractility by ouabain after the pretreatment of 6-hydroxydopamine and alpha-methyl-p-tyrosine was reduced to 16.7% and 50.3% of the control, respectively. The results obtained suggest that catecholamines in the myocardium play some important role in producing cardiotonic action of cardiac glycosides. Brain catecholamines or the central sympathetic nervous system do not appear to participate in the exertion of the positive inotropic action of cardiac glycosides. (+info)
Evidence for a dual innervation affecting local blood flow in the hypothalamus of the conscious rabbit.
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We have attempted to evaluate the role of adrenergic nerves which arise from the superior cervical ganglia or which are intracerebral throughout their course, in the control of local cerebral blood flow (CBF). Hypothalamic blood flow (HBF) was measured in the conscious rabbit by the 133Xe-clearance technique. Stimulation of the upper brainstem, using 5-Hz, 3-V, 1-msec, square wave pulses, increased by HBF by a mean of 7.6 ml/100 g per min (P less than 0.005). This effect was abolished by the intrahypothalamic injection of the beta-adrenoreceptor blocker, propranolol, and by chemical sympathectomy of the hypothalamus or of the upper brainstem with 6-hydroxydopamine, but was not altered by bilateral cervical ganglionectomy. Intrahypothalamic injection of 0.1 mug of tyramine caused a mean decrease in HBF of 15.6 ml/100 g per min (P less than 0.001). This effect of intrahypothalamic injection of tyramine was abolished by bilateral cervical sympathectomy but not by chemical sympathectomy of the upper brainstem. These results support the idea that local CBF, at least in the hypothalamus, is mediated by two distinct pathways. The first consists of the sympathetic nerves which arise in the cervical ganglia, and which activate intrahypothalamic alpha-receptors to cause constriction. The second is an entirely intracerebral noradrenergic pathway which stimulates beta-receptors to cause vasodilation. (+info)
The effects of intra-amygdaloid injections of 6-hydroxy-dopamine on avoidance responding in rats.
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1 The effects of bilateral intra-amygdaloid injections of 6-hydroxydopamine (6-OHDA) on shuttle box avoidance acquisition, retention, and extinction, and passive avoidance acquisition were examined in rats. 2 Intra amygdaloid 6-OHDA injections produced catecholamine depletion in and around the amygdalae but failed to reduce striatal dopamine concentrations. 3 Conditioned avoidance acquisition was markedly inhibited in 6-OHDA-treated rats whereas retention and extinction were only slightly impaired. 4 Passive avoidance acquisition was slightly but significantly improved in rats with amygdaloid 6-OHDA lesions. 5 Treated rats showed no motor abnormalities, they were not hypoactive in a photocell activity cage and they performed as well as controls on a rotating rod. 6 It is suggested that the conditioned avoidance acquisition deficit in rats with amygdaloid 6-OHDA lesions may be related to an impairment of associative learning rather than to perceptual or motor disturbances. (+info)
The uptake of tritiated delta 1-tetrahydrocannabinol by the isolated vas deferens of the rat.
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1 Weighed stripped vasa deferentia were incubated in Holman's solution containing (a) [14C]-sorbitol 0.014 mm, (b) [3H]-noradrenaline ([3H]-NA) 12.31 nM, (c) [3H]-tetrahydrocannabinol ([3H]-delta1-THC) 1 mug/ml for 5, 10, 20 and 30 minutes. 2 Tissues were washed, dissolved in Protosol, counted by standard scintillation counting technique and 'drug space' expressed as ct min-1 mg-1 tissue/ct min-l mul-1 bathing fluid. 3 Vasa incubated for 30 min with [14C]-sorbitol were washed for varying lengths of time; 82% clearance had taken place after 2 washes of 5 minutes. 4 The uptake of [3H]-NA was inhibited by the presence of desmethylimipramine (DMI) 10 nM in the bath or by pretreatment of rats with 6-hydroxydopamine (6-OHDA). 5 The uptake of [3H]-delta 1-THC was not inhibited by the presence of DMI. It was reduced but not abolished by 6-OHDA pretreatment. (+info)
Mechanism of the indirect sympathomimetic effect of 5-hydroxytrypt-amine on the isolated heart of the rabbit.
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1 Rabbit isolated hearts, perfused by the Langendorff technique, were used to investigate the indirect sympathomimetic effects of 5-hydroxytryptamine (5-HT). Comparisons were made with noradrenaline and with two indirectly acting sympathomimetic agents with entirely different mechanisms of action, tyramine and dimethylphenylpiperazinium (DMPP). 2 The cardiac stimulant effects of 5-HT, tyramine and DMPP were inhibited by propranolol and practolol and the pA2 values obtained were similar to those obtained with noradrenaline as the agonist. 3 Responses to 5-HT, tyramine and DMPP were greatly reduced on hearts from rabbits pretreated with 6-hydroxydopamine. Such hearts had less than 7% of their normal catecholamine concentration and no fluorescence characteristic of noradrenaline in the cardiac sympathetic nerves could be demonstrated. 4 Rapid, reversible and selective tachyphylaxis to 5-HT was demonstrated during perfusion with 5-HT. In hearts desensitized to DMPP by perfusion with DMPP, responses to 5-HT were also reduced. 5 Perfusion of hearts with colchicine inhibited stimulant responses to 5-HT and DMPP but had little effect on responses to noradrenaline or tyramine. 6 Desmethylimipramine enhanced cardiac stimulant responses to noradrenaline and to a lesser extent, those to 5-HT and DMPP. Responses to tyramine were consistently inhibited by desmethylimipramine. 7 Tetrodotoxin abolished responses of the heart to electrical nerve stimulation but left responses to noradrenaline, 5-HT and DMPP unaffected. 8 5-HT, tyramine and DMPP evoked 3H-release from hearts whose neuronal noradrenaline stores had been labelled by perfusion with [3H]-(-)-noradrenaline. The pattern of release evoked by 5-HT was similar to that of DMPP but differed from that of tyramine. 9 Reducing the calcium concentration in the Tyrode solution from 3.6 to 0.2 mEq/1 did not affect 3H-overflow after tyramine but greatly inhibited that evoked by 5-HT and DMPP. 10 The results confirm that the stimulatn effects of 5-HT on the rabbit isolated heart are the result of noradrenaline release. They further suggest that the site of the release is the terminal sympathetic nerve network. The mechanism of release shows more similarities to that of DMPP (calcium-dependent depolarization and exocytosis) than to that of tyramine (neuronal uptake and stoichiometric displacement). (+info)