Selective vascular permeability to digoxin and the inhibition of Na+,K+ adenosine triphosphatase in the brain stem

Bass, Norman H.; Traurig, Harold H.; Mann, J.D.

doi:10.1016/0014-4886(82)90078-4

Cited by 3 publications

(8 citation statements)

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“…In addition, the present results complement our previous observations in digoxin-treated rats which demonstrated a significant inhibition of Na+, K + ATPase activity in sections of medulla at the level of the area postrema (Bass et al, 1982). Together, these in vivo studies suggest that the area postrema may constitute a portal of entry for cardiac glycosides into the brainstem that bypasses the blood-brain barrier.…”

Section: Discussionsupporting

confidence: 91%

“…Frazier and Binnion (1981) reported a significant uptake of 3H-digoxin in the region of the area postrema of the canine medulla compared with cerebral cortex. Bass et al (1982) reported similar results with 3H-digoxin in the rat. Earlier, Donaldson et al (1972) also observed accumulation of radioactivity in the medulla of the rat following intraventricular injection of 3H-ouabain.…”

Section: Discussionsupporting

confidence: 88%

“…2B,C, 3A) may be related to these processes. Neuron cell bodies have been identified in area postrema (Brizzee and Neal, 1954;Morest, 1960Morest, , 1967Dempsey, 1973;Klara et al, 1978;Kalia and Sullivan, 1982), suggesting an important interaction between the chemosensory function of area postrema and the nucleus solitarius (Frazier and Binnion, 1981;Bass et al, 1982;Kalia and Sullivan, 1982;van der Kooy and Koda, 1983). Possibly the labeled cells observed in the area postrema in this study (Figs.…”

Section: Discussionmentioning

confidence: 72%

“…Somberg and Smith (1979) have concluded that this chronotropic effect on the heart by cardiac glycoside was due to an activation of parasympathetic nuclei and reflex inhibition of sympathetic centers in the medulla. Our previous studies led to the conclusion that the area postrema, which lacks a bloodbrain barrier, serves as a portal of entry into the medulla for blood-borne cardiac glycosides which then may bind to specific, high affinity sites on cells in regions known to modulate cardiac rhythm (Bass et al, 1982). Pace and Gillis (1982) have reached a similar conclusion.…”

Section: Discussionmentioning

confidence: 87%

“…This has led several investigators to suggest that the portal of entry for blood-borne cardiac glycosides into the medulla may be the area postrema (Levitt et al, 1973;Somberg and Smith, 1979;Bass et al, 1982;Pace and Gillis, 1982)-a brain region long known to lack a blood-brain barrier (Brizzee and Neal, 1954;Roth and Yamamoto, 1968;Torack and Finke, 1971).…”

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confidence: 97%

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Autoradiographic localization of ³H‐digoxin binding by neural cells in the medulla

1985

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The purpose of this investigation was to localize binding sites for the cardiac glycoside digoxin in the medulla of the rat in vivo. Adult male Sprague-Dawley rats were injected (IV) with 3H-digoxin and killed 30 minutes later. Autoradiographs of medullas showed evidence of 3H-digoxin binding to small- and medium-sized neural cells in the regions of the nucleus solitarius, dorsal motor nucleus of the vagus, area postrema, and in the zone between the area postrema and the underlying neuropil. However, the parasympathetic preganglionic neurons of the dorsal motor nucleus were not labeled. The 3H-digoxin-labeled cells in the medulla were located mainly in the commissural and medial portions of nucleus solitarius at the level of the area postrema. Animals injected with unlabeled digoxin followed by 3H-digoxin showed reduced binding of radioactivity. The small- and medium-sized neurons of the caudal portions of the nucleus solitarius are internuncial in position with respect to cardiovascular afferents of the glossopharyngeal and vagus nerves and sympathetic and parasympathetic cardiovascular efferent neurons of the medulla. The results of this study suggest that these 3H-digoxin-labeled cells, presumably neurons of nucleus solitarius, may possess high affinity binding sites for digoxin. Further, the area postrema, which lacks a blood-brain barrier, may provide a portal of entry for 3H-digoxin into regions of the medulla known to contain neurons that play a role in the regulation of cardiac rhythm.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 97%

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Autoradiographic localization of ³H‐digoxin binding by neural cells in the medulla

1985

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Controversies in the Actions of Digitalis Substances: Are all Digitalis Derivatives Alike?

Lathers¹,

Lipka²,

Klions³

1985

The Journal of Clinical Pharma

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Digitalis Glycosides: A Discussion of the Similarities and Differences in Actions and Existing Controversies

Lathers

Lipka²,

Klions³

1988

Journal of Basic and Clinical Physiology and Pharmacology

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The writing of this review was initiated to answer the question of whether differences in the actions of the various digitalis glycosides exist and to discuss current controversies in the research area of the digitalis glycosides. Data obtained in our laboratory /1,2/ indicated that the effect of digoxin on postganglionic cardiac sympathetic neural discharge in the minute prior to the occurrence of arrhythmia differed from that of ouabain. This raised the question of whether data published in other laboratories would support the contention that differences in glycosides do exist. To answer this question, a review of the literature was begun. Our survey of these studies are cited in the tables of this review. These tables summarize the actions of glycosides in vivo and in vitro in different animal models. The reader should bear in mind that the data included within the tables do not represent an inclusive summary of all studies in the literature. For detailed review articles, the reader is referred to the following references: Gillis et al /3/; Gillis and Quest /4/; Roberts et al /5/; Lathers and Roberts /6/; Farah and Alousi /7/; Benthe /8/; Levitt et al /9/; Smith and Haber /10/; Somberg /ll/; Lee and Klaus /12/; Mason /13/; Schwartz /14·/. Furthermore the summary of the results for each particular study cited in the table may not, in all cases, include each finding of the published data. Nevertheless, the tables do provide a summary of data obtained in various species with different glycosides in several different areas of research, and as such, represent an abridged compendium for the researcher working in the field of digitalis glycosides. This review has been organized firstly to consider glycoside-induced alterations in the autonomic nervous system and, secondly, to examine their direct actions on the heart. Introduction Autonomic Nervous System A. Peripheral Sites The effect of digitalis glycosides on pre-and postganglionic cardiac sympathetic and parasympathetic nervesThe concept of a neural component in the pharmacology of digitalis glycosides is more than a century old /15,16/. The possibility of a peripheral but still nerve related site of action for digitalis glycosides was recognized butcontrol 20 40 60 80 100 control 20 40 60 80 100 % of Arrhythmoganic Dot· DIGITOXIN Spinal, Vagotomized I70r DIGOXIN Spinal, Vofotomizttf Fig. 2: The effect of digitoxin (left panels) or digoxin infusion* (right panels) on heert rate of animals with spinal cords transected with (lower panels) and without (upper panels) bilateral vagotomy. Upper Panel -Each point represents the average response of 9 animals. The vertical bars indicate standard errors. Lower Panel -Each point represents the average response of 8 animals. The vertical bars indicate standard errors. Modified from Pace et el., Eur J Pharmacol 1974; 28: 2881221. a. Quinidine When considering the action of glycosides, one question which should be asked is whether the ability of all digitalis glycosides to produce cardiac 8 Brought to you by | New York Univers...

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Selective vascular permeability to digoxin and the inhibition of Na+,K+ adenosine triphosphatase in the brain stem

Cited by 3 publications

References 31 publications

Autoradiographic localization of ³H‐digoxin binding by neural cells in the medulla

Autoradiographic localization of ³H‐digoxin binding by neural cells in the medulla

Controversies in the Actions of Digitalis Substances: Are all Digitalis Derivatives Alike?

Digitalis Glycosides: A Discussion of the Similarities and Differences in Actions and Existing Controversies

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Selective vascular permeability to digoxin and the inhibition of Na+,K+ adenosine triphosphatase in the brain stem

Cited by 3 publications

References 31 publications

Autoradiographic localization of 3H‐digoxin binding by neural cells in the medulla

Autoradiographic localization of 3H‐digoxin binding by neural cells in the medulla

Controversies in the Actions of Digitalis Substances: Are all Digitalis Derivatives Alike?

Digitalis Glycosides: A Discussion of the Similarities and Differences in Actions and Existing Controversies

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Autoradiographic localization of ³H‐digoxin binding by neural cells in the medulla

Autoradiographic localization of ³H‐digoxin binding by neural cells in the medulla