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Title: Membrane events and ionic processes involved in dopamine release from tuberoinfundibular neurons. II. Effect of the inhibition of the Na+-Ca++ exchange by amiloride

Abstract

In the present study we investigated the effect of amiloride, a rather specific inhibitor of the membrane Na+-Ca++ exchange system, on the release of endogenous dopamine (DA) and previously taken-up (3H)DA from tuberoinfundibular dopaminergic neurons. Amiloride (300 microM) stimulated either endogenous DA or (3H)DA release. Amiloride-induced stimulation of (3H)DA release was prevented in a Ca++-free plus ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid medium. Amiloride, at the same concentration, reinforced both high K+- and electrically-induced stimulation of (3H)DA release. These results are explained on the basis of the ability of amiloride in blocking the Na+-Ca++ exchange system, therefore causing an elevation of intracellular Ca++ levels in resting conditions, and a further accumulation of Ca++ ions after high K+- or electrically elicited opening of voltage-operated channels specific for Ca++ ions. The enhanced intracellular Ca++ availability may trigger the stimulation of neurotransmitter release. In addition, amiloride was able to block in a dose-dependent manner (70-300 microM) the ouabain-induced (3H)DA release, suggesting that, when intracellular concentrations of Na+ are increased by the blockade of Na+,K+-adenosine triphosphatase the Na+-Ca+;+ exchange carrier reverses its resting mode of operation, mediating the influx of extracellular Ca++ ions. Amiloride, by blocking the Na+-Ca++ exchange mechanism, prevents the ouabain-elicited entrance ofmore » extracellular Ca++ ions, therefore inhibiting (3H)DA release stimulated by the cardioactive glycoside. Collectively, the results of the present study seem to be compatible with the idea that the Na+-Ca++ exchange mechanism is involved in the regulation of (3H)DA release from tuberoinfundibular dopaminergic neurons, through the regulation of Ca++ movements across the plasma membrane.« less

Authors:
; ; ; ;
Publication Date:
Research Org.:
Unive. of Naples (Italy)
OSTI Identifier:
6805328
Resource Type:
Journal Article
Resource Relation:
Journal Name: J. Pharmacol. Exp. Ther.; (United States); Journal Volume: 246:2
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CALCIUM COMPOUNDS; MEMBRANE TRANSPORT; DIURETICS; BIOLOGICAL EFFECTS; DOPAMINE; SECRETION; SODIUM COMPOUNDS; ATP-ASE; CATIONS; CELL MEMBRANES; HYPOTHALAMUS; IN VITRO; INHIBITION; ION EXCHANGE; OUABAIN; RATS; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ACID ANHYDRASES; ALKALI METAL COMPOUNDS; ALKALINE EARTH METAL COMPOUNDS; AMINES; ANIMALS; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; BODY; BRAIN; CARBOHYDRATES; CARDIAC GLYCOSIDES; CARDIOTONICS; CARDIOVASCULAR AGENTS; CELL CONSTITUENTS; CENTRAL NERVOUS SYSTEM; CHARGED PARTICLES; DRUGS; ENZYMES; GLYCOSIDES; HYDROLASES; HYDROXY COMPOUNDS; IONS; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; MAMMALS; MEMBRANES; NERVOUS SYSTEM; NEUROREGULATORS; ORGANIC COMPOUNDS; ORGANS; PHENOLS; PHOSPHOHYDROLASES; POLYPHENOLS; RODENTS; STROPHANTHINS; SYMPATHOMIMETICS; VERTEBRATES 550201* -- Biochemistry-- Tracer Techniques

Citation Formats

Taglialatela, M., Amoroso, S., Canzoniero, L.M., Di Renzo, G.F., and Annunziato, L.. Membrane events and ionic processes involved in dopamine release from tuberoinfundibular neurons. II. Effect of the inhibition of the Na+-Ca++ exchange by amiloride. United States: N. p., 1988. Web.
Taglialatela, M., Amoroso, S., Canzoniero, L.M., Di Renzo, G.F., & Annunziato, L.. Membrane events and ionic processes involved in dopamine release from tuberoinfundibular neurons. II. Effect of the inhibition of the Na+-Ca++ exchange by amiloride. United States.
Taglialatela, M., Amoroso, S., Canzoniero, L.M., Di Renzo, G.F., and Annunziato, L.. 1988. "Membrane events and ionic processes involved in dopamine release from tuberoinfundibular neurons. II. Effect of the inhibition of the Na+-Ca++ exchange by amiloride". United States. doi:.
@article{osti_6805328,
title = {Membrane events and ionic processes involved in dopamine release from tuberoinfundibular neurons. II. Effect of the inhibition of the Na+-Ca++ exchange by amiloride},
author = {Taglialatela, M. and Amoroso, S. and Canzoniero, L.M. and Di Renzo, G.F. and Annunziato, L.},
abstractNote = {In the present study we investigated the effect of amiloride, a rather specific inhibitor of the membrane Na+-Ca++ exchange system, on the release of endogenous dopamine (DA) and previously taken-up (3H)DA from tuberoinfundibular dopaminergic neurons. Amiloride (300 microM) stimulated either endogenous DA or (3H)DA release. Amiloride-induced stimulation of (3H)DA release was prevented in a Ca++-free plus ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid medium. Amiloride, at the same concentration, reinforced both high K+- and electrically-induced stimulation of (3H)DA release. These results are explained on the basis of the ability of amiloride in blocking the Na+-Ca++ exchange system, therefore causing an elevation of intracellular Ca++ levels in resting conditions, and a further accumulation of Ca++ ions after high K+- or electrically elicited opening of voltage-operated channels specific for Ca++ ions. The enhanced intracellular Ca++ availability may trigger the stimulation of neurotransmitter release. In addition, amiloride was able to block in a dose-dependent manner (70-300 microM) the ouabain-induced (3H)DA release, suggesting that, when intracellular concentrations of Na+ are increased by the blockade of Na+,K+-adenosine triphosphatase the Na+-Ca+;+ exchange carrier reverses its resting mode of operation, mediating the influx of extracellular Ca++ ions. Amiloride, by blocking the Na+-Ca++ exchange mechanism, prevents the ouabain-elicited entrance of extracellular Ca++ ions, therefore inhibiting (3H)DA release stimulated by the cardioactive glycoside. Collectively, the results of the present study seem to be compatible with the idea that the Na+-Ca++ exchange mechanism is involved in the regulation of (3H)DA release from tuberoinfundibular dopaminergic neurons, through the regulation of Ca++ movements across the plasma membrane.},
doi = {},
journal = {J. Pharmacol. Exp. Ther.; (United States)},
number = ,
volume = 246:2,
place = {United States},
year = 1988,
month = 8
}
  • In the present study we investigated the membrane events and the ionic processes which mediate the stimulatory effect of ouabain on the release of endogenous dopamine (DA) and previously taken-up (3H)DA release from rat hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons. Ouabain (0.1-1 mM) dose-dependently stimulated endogenous DA and newly taken-up (3H)DA release. This effect was counteracted partially by nomifensine (10 microM). Removal of Ca++ ions from the extracellular space in the presence of the Ca++-chelator ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid prevented completely ouabain-elicited (3H)DA release. Lanthanum (1 mM) and cobalt (2 mM), two inorganic Ca++-entry blockers, were able to inhibit thismore » stimulatory effect, whereas verapamil (10 microM) and nitrendipine (50 microM), two organic antagonists of the voltage-operated channel for Ca++ ions, failed to affect ouabain-induced (3H)DA release. By contrast, adriamycin (100-300 microM), a putative inhibitor of cardiac Na+-Ca++ antiporter, dose-dependently prevented ouabain-induced (3H)DA release from TIDA neurons. Finally, tetrodotoxin reduced digitalis-stimulated (3H)DA release. In conclusion, these results seem to be compatible with the idea that the inhibition of Na+,K+-adenosine triphosphatase by ouabain stimulates the release of (3H)DA from a central neuronal system like the TIDA tract and that this effect is critically dependent on the entrance of Ca++ ions into the nerve terminals of these neurons. In addition the Na+-Ca++ exchange antiporter appears to be the membrane system which transports Ca++ ions into the neuronal cytoplasm during Na+,K+-adenosine triphosphatase inhibition. The enhanced intracellular Ca++ availability triggers DA release which could occur partially through a carrier-dependent process.« less
  • The mechanism by which terminal guanidino nitrogen substituted analogues of amiloride inhibit Na-Ca exchange in purified cardiac sarcolemmal membrane vesicles has been investigated. These inhibitors block both Na/sub i/-dependent Ca/sup 2 +/ uptake and Na/sub 0/-dependent Ca/sup 2 +/ efflux. Inhibition of Na-Ca exchange monitored in K/sup +/ is noncompetitive vs /sup 45/Ca/sup 2 +/ but competitive vs /sup 22/Na/sup +/. Substitution of sucrose for K/sup +/ results in mixed kinetics of inhibition vs /sup 45/Ca/sup 2 +/, suggesting a complex interaction between inhibitor and carrier under this condition. Amiloride derivatives also block two other modes of carrier action: Na-Namore » exchange is inhibited in a competitive fashion with Na/sup +/ and kinetics of Ca-Ca exchange inhibition are mixed vs Ca/sup 2 +/ in either sucrose or K/sup +/. However, Ca-Ca exchange inhibition can be alleviated by increasing K/sup +/ concentration. Dixon analyses of Na-Ca exchange block with mixtures of inhibitors suggest that these agents are interacting at more than one site. In addition, Hill plots of inhibition are biphasic with Hill coefficients of 1 and 2 at low and high inhibitor concentration, respectively. These results indicate that amiloride derivatives are mechanisms-based inhibitors that interact at two classes of substrate-binding sites on the carrier; at low concentration they bind preferentially to a site that is exclusive for Na/sup +/, while at higher concentration they also interact at a site that is common for Na/sup +/, Ca/sup 2 +/, and K/sup +/« less
  • Prolonged exposure to estradiol 17-..beta.. (E/sub 2/) in rats has been shown to decrease dopamine (DA) synthesis in and release from tuberoinfundibular dopaminergic (TIDA) neurons in Fischer 344 rats. The objective of the present study was to determine whether inhibition of the E/sub 2/-induced increase in anterior pituitary (AP) weight and prolactin (PRL) secretion by concomitant administration of the dopaminergic agonist, bromocryptine, could prevent the decrease in TIDA neuronal function produced by chronic E/sub 2/ administration. TIDA neuronal function was evaluated by in vitro superfusion and electrical stimulation of median eminence (ME) tissue after allowing for accumulation of (/sup 3/H)more » dopamine (DA). The effect of chronic E/sub 2/ and/or bromocryptine treatment on catecholamine content in tuberohypophyseal neurons in the neurointermediate lobe was also measured to determine whether increased pituitary size possibly damaged the tuberohypophyseal neurons.« less
  • The anatomical relationships between endorphinic neurons and dopaminergic neurons were evaluated in the rat hypothalamus using a combination of immunocytochemistry and autoradiography. In the arcuate nucleus, endorphinic endings were seen making contacts with dopaminergic cell bodies and dendrites. No synapsis could be observed at the sites of contacts. These results strongly suggest that the endorphinic neurons are directly acting on dopaminergic neurons to modify the release of dopamine into the pituitary portal system.
  • Dopamine-sensitive adenylate cyclase and TH-SCH 23390 binding parameters were measured in the rat substantia nigra and striatum 15 days after the injection of 6-hydroxydopamine into the medial forebrain bundle. The activity of nigral dopamine-sensitive adenylate cyclase and the binding of TH-SCH 23390 to rat nigral D-1 dopamine receptors were markedly decreased after the lesion. On the contrary, 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine pathway enhanced both adenylate cyclase activity and the density of TH-SCH 23390 binding sites in striatal membrane preparations. The changes in TH-SCH 23390 binding found in both nigral and striatal membrane preparations were associated with changes inmore » the total number of binding sites with no modifications in their apparent affinity. The results indicate that: a) within the substantia nigra a fraction (30%) of D-1 dopamine receptors coupled to the adenylate cyclase is located on cell bodies and and/or dendrites of dopaminergic neurons; b) striatal D-1 dopamine receptors are tonically innervated by nigrostriatal afferent fibers. 24 references, 1 figure, 1 table.« less