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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 333 (1986), S. 7-12 
    ISSN: 1432-1912
    Keywords: Heart ; Parasympathetic nervous system ; Ouabain ; Release of acetylcholine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the study was to elucidate peripheral effects of ouabain on the parasympathetic innervation of the heart, effects that could contribute to the experimentally and clinically well established “vagal effect of cardiac glycosides”. The experiments were carried out with ouabain concentrations of 3×10−7 and 10−6 mol/l, which were considered “therapeutic”, as they increased force of contraction and did not elicit arrhythmias in incubated chicken atria. In atrial preparations of chickens and guinea-pigs the negative chronotropic and inotropic effects of acetylcholine (ACh) were not altered by 3×10−7 mol/l ouabain. Resting efflux of ACh from perfused chicken hearts was increased by ouabain from 10 to a maximum of 30 pmol/g min, whereas release of ACh evoked by bilateral vagal stimulation at 3 or 20 Hz for 1 min was unchanged (resting release subtracted). In contrast, release of ACh caused by unilateral vagal stimulation was augmented by ouabain up to 200% of the control. Release by unilateral stimulation (80 pmol/g; 20 Hz) was calculated for each experiment by averaging the releases evoked by consecutive stimulation of the right and left nerves. Ouabain infused for 90 min did not alter the tissue content of ACh (5.5 nmol/g). Within 2 days after unilateral (left) vagal transsection (denervation of cardiac ganglia) the release of ACh evoked by stimulation of the intact nerve (20 Hz) increased from about 80 to 200 pmol/g, whereas the release from the lesioned nerve markedly declined. One day after denervation, ouabain had lost the ability to facilitate the release of ACh evoked by stimulation of the intact nerve, whereas the release by stimulation of the lesioned nerve was still increased. It is concluded that ouabain at “therapeutic” concentrations increased resting release of ACh but did not influence the mechanism of action potential-evoked release of ACh. The effect of exogenous ACh on sinus node activity was not enhanced by ouabain. The observation that ouabain increased release of ACh caused by unilateral, but not by bilateral vagal stimulation was explained by an increase in the number of activated postganglionic neurons arising from those (contralateral) ganglia that received a subthreshold input from the stimulated vagus nerve.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 301 (1978), S. 207-215 
    ISSN: 1432-1912
    Keywords: Release of acetylcholine ; Choline ; Physostigmine ; Isolated heart ; Parasympathetic ganglionic transmission
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The concentrations of acetylcholine, choline and noradrenaline were estimated in the perfusate (overflow) of isolated hearts of chickens, cats, rabbits and guinea pigs. Neurotransmitter release was evoked by stimulation of both vagus nerves and by direct stimulation of the heart (field stimulation). 2. In the absence of exogenous choline and physostigmine, field stimulation at 20 Hz for 20 min caused an overflow of acetylcholine from the hearts of the 4 species investigated. During vagal stimulation, however, acetylcholine was detected only in the perfusate of the chicken heart. 3. Field stimulation for 2 min caused an overflow of 193 pmol g−1 min−1 acetylcholine and of 666 pmol g−1 min−1 noradrenaline from the guinea pig heart; pretreatment of the animals with reserpine blocked the release of noradrenaline but left the overflow of acetylcholine unaltered. 4. When the overflow of acetylcholine was evoked by vagal stimulation, infusion of 10−5 M choline into the cat and chicken heart caused an increase in the overflow that was 2–3-fold in the chicken heart and at least 23-fold in the cat heart (23 times the limit of estimation). In the presence of choline, the overflow of acetylcholine from the hearts of the 4 species evoked by field stimulation was 2–3 times the overflow in the absence of the drug. 5. Inhibition of the cholinesterase activity by 10−6 M physostigmine raised the overflow of acetylcholine evoked by vagal and/or by field stimulation uniformly by a factor of 2 to 3 in the 4 species investigated. In the cat heart, the combination of 10−5 M choline and 10−6 M physostigmine increased the overflow evoked by field stimulation for 20 min from 0.54 to 3.6 nmol g−1 20 min−1, i.e. by a factor of 7. 6. The cardiac content of acetylcholine was highest in the chicken heart (9.8 nmol/g) and lowest in the guinea pig heart (2.1 nmol/g). 7. The spontaneous efflux of choline from the isolated hearts after 15 min of perfusion ranged from 0.4 (cat) to 2.1 nmol g−1 min−1 (chicken) and was maintained at these levels for at least 1 h. 8. In the blood of chickens, cats and rabbits, the choline concentration was 0.5–1.0×10−5 M. 9. It is concluded that (1) an appreciable amount of acetylcholine released from parasympathetic nerves escapes into the circulation of isolated hearts, (2) the extent of the extracellular hydrolysis of acetylcholine is the same in avian and mammalian hearts, (3) the release of acetylcholine evoked by vagal stimulation is much smaller in the isolated cat heart than that in the chicken heart, because of an insufficient ganglionic transmission due to a deficiency in extracellular choline and finally (4) the amount of acetylcholine released by vagal stimulation is dependent on both the efflux of choline from extraneuronal sources and the overall density of the cholinergic innervation of the heart.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0878
    Keywords: Adrenal medulla (rat) ; Vinblastine ; Ultrastructure ; Catecholamines ; Enzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effects of a single high dose (10mg/kg) of vinblastine (vb) sulfate (“Velbe”, Lilly) on the ultrastructure, catecholamine (CA) content and activity of CA-synthesizing enzymes of the rat adrenal medulla were studied for up to 120h after intravenous injection of the drug. By 1 h, microtubules were virtually absent from chromaffin cells and preganglionic cholinergic axons, and typical paracrystals had appeared inside the nerve fibers. By 16h microtubules were completely reconstituted and paracrystals had disappeared. From 16h onwards, there was an increasing depletion of storage granules from adrenaline (A) — producing cells, which coincided with biochemical determinations showing a reduction of adrenal A to about 40 % of control levels by 48 h, with noradrenaline (NA) remaining in the range of controls. Both A- and NA-storing cells showed an extensive proliferation of the rough endoplasmic reticulum (ER). Vb caused a marked increase in tyrosine hydroxylase (TH; +113%) and dopamine β-hydroxylase (DBH; +82%) activities after 48 h. Splanchnicotomy completely abolished the vb-mediated increase in TH and DBH activities. A smaller increase (+ 47 %) in enzyme activity was observed with phenylethanolamine N-methyltransferase (PNMT). Vb (10−5M) had no apparent effect on granule content and the amount of rough ER in chromaffin cells, which were cultured for 48 h. The results demonstrate that a single high dose of vb has relatively little short-term effects on the rat adrenal medulla, but causes drastic long-term changes in CA-content and enzyme activities that are mediated by the preganglionic nerves. These changes could be interpreted as an effort to compensate for a loss of CA-stores in peripheral adrenergic nerves (cf. Cheney et al., 1973). The differential long-term effect of vb on adrenal NA and A might be due to the lower induction of PNMT as compared to TH and DBH activities and/or to a preferential release of A versus NA, which may occur at high frequencies of stimulation of the splanchnic nerves.
    Type of Medium: Electronic Resource
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