Abnormal sodium transport in synaptosomes from brain of uremic rats.

Fraser, C. L.; Sarnacki, P.; Arieff, Allen I.

doi:10.1172/jci111920

Cited by 48 publications

(31 citation statements)

References 40 publications

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“…An assay of uptake in freshly prepared synaptosomes from rats with 48 h of hypernatremic dehydration demonstrated a 17% increase in Na+-specific taurine transport compared to synaptosomes isolated from control animals. The stability of synaptosomal taurine uptake in stored vesicles is in accord with previous work investigating cerebral ion transport in which frozen synaptosomes were used (12).…”

Section: Resultssupporting

confidence: 81%

“…These features were virtually identical to those reported by Fraser et al (12). Thus, passive uptake into synaptosomes of varying size or transport by contaminating organelle membranes cannot account for the differences in taurine transport between hypernatremic and control animals.…”

Section: -Chd Chronic Hypernatremic Dehydrationsupporting

confidence: 87%

“…Synaptosomes were isolated according to the procedure described by Fraser et al (12). Brains were minced with a scalpel, washed three times to remove blood and extraneous tissue fragments, brought up to 15 mL with isolation medium, and then homogenized with 15 strokes of a glass Dounce homogenizer (Wheaton, Millville, NJ).…”

Section: Animalsmentioning

confidence: 99%

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Taurine and Osmoregulation. IV. Cerebral Taurine Transport Is Increased in Rats with Hypernatremic Dehydration

1992

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ABSTRACT. Taurine is an organic osmolyte in brain cells. We studied whether cerebral taurine transport is enhanced as part of the cell volume regulatory adaptation to hypernatremia. Hypernatremic dehydration was induced for 48 h. Synaptosomes, metabolically active nerve terminal vesicles, were isolated by homogenization of brain and purification on a discontinuous Ficoll gradient. Taurine transport was evaluated in vitro using a rapid filtration assay. After 48 h of hypernatremia, there was a 22.4% increment in Na+-specific taurine transport from 2.99 f 0.16 to 3.66 2 0.13 pmollmg protein130 min (p < 0.001). Dehydration for 48 h without hypertonic saline loading had no effect on taurine uptake. Glycine transport was unaltered by hypernatremia. The adaptation in taurine uptake resulted from an enhanced V,,, of the high affinity-low capacity transport system [265 +: 17, control versus 337 f 19 nmol/min/ mg protein, experimental ( p < 0.03)] without a change in the Km (260 pM). Under both control and hypernatremic conditions, Na+ and C1-were required for maximal total Na+-mediated taurine uptake. Oubain (1 mM) decreased taurine uptake by 25%, whereas addition of B-alanine or hypotaurine (500 pM) to the external media reduced taurine transport by 4 5 6 5 % in both control and experimental conditions ( p < 0.01). Synaptosomal taurine uptake in hypernatremic rats was inhibited by 1 5 2 0 % (p c 0.01) after addition of 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (0.1 mM) or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (0.1 mM) to the external medium. We conclude that hypernatremic dehydration of moderate severity and duration results in stimulation of brain taurine uptake, mediated by increased activity of the B-amino acid carrier. An intact anionic binding site is required for maximal taurine uptake during hypernatremia.

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Section: Resultssupporting

confidence: 81%

Section: -Chd Chronic Hypernatremic Dehydrationsupporting

confidence: 87%

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Taurine and Osmoregulation. IV. Cerebral Taurine Transport Is Increased in Rats with Hypernatremic Dehydration

1992

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“…In a limited number of other tissues (9)(10)(11)(12), there is evidence that sodium pump activity may be abnormal in uremia, and in skeletal muscle of dialysis patients, there is an abnormally low resting membrane potential and increased intracellular sodium, consistent with a defect in sodium pump function (13). Despite these reports, it cannot be concluded that in uremia, all tissues will exhibit the same pathophysiology for defective basal and/or hormonally stimulated active sodium transport.…”

Section: Introductionmentioning

confidence: 99%

Abnormal cation transport in uremia. Mechanisms in adipocytes and skeletal muscle from uremic rats.

Druml¹,

Kelly²,

May³

et al. 1988

J. Clin. Invest.

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The cause of the abnormal active cation transport in erythrocytes of some uremic patients is unknown. In isolated adipocytes and skeletal muscle from chronically uremic chronic renal failure rats, basal sodium pump activity was decreased by 36 and 30%, and intracellular sodium was increased by 90 and 50%, respectively, compared with pair-fed control rats; insulin-stimulated sodium pump activity was preserved in both tissues. Lower basal NaK-ATPase activity in adipocytes was due to a proportionate decline in PHiouabain binding, while in muscle, I3HJouabain binding was not changed, indicating that the NaK-ATPase turnover rate was decreased. Normal muscle, but not normal adipocytes, acquired defective Na pump activity when incubated in uremic sera. Thus, the mechanism for defective active cation transport in CRF is multifactorial and tissue specific. Sodium-dependent amino acid transport in adipocytes closely paralleled diminished Na pump activity (r = 0.91), indicating the importance of this defect to abnormal cellular metabolism in uremia.

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“…We observed abnormal extracellular amino acid neurotransmitter concentrations in the mediobasal hypothalamus of uremic rats, compatible with disturbed regulation of hypothalamic neurons by higher neuronal centers (6). The function of brain synaptosomes is altered in experimental uremia (7)(8)(9)(10). However, we also demonstrated direct inhibition of GnRH secretion from cultured hypothalamic neurons by a factor circulating in uremic serum (11).…”

mentioning

confidence: 99%

Impaired Autofeedback Regulation of Hypothalamic Norepinephrine Release in Experimental Uremia

Klein

Daschner

Vogel

et al. 2005

Journal of the American Society of Nephrology

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Chronic renal failure (CRF) is associated with multiple hypothalamic dysfunctions, including reduced secretion of gonadotropin-releasing hormone (GnRH). Because GnRH release is tightly controlled by sympathetic neuronal input, a possible alteration of local noradrenergic neurotransmission in experimental CRF was evaluated. Basal, stimulated, and autoinhibited norepinephrine (NE) release was assessed in hypothalamic and hippocampal tissue slices obtained from 5/6-nephrectomized and control rats. Autoinhibition-free NE release from brain slices, prelabeled with [ 3 H]NE and superfused with physiologic buffer, was stimulated by six electrical pulses, 100 Hz (pseudo-one-pulse stimulation). Autoinhibited NE release was induced by 90 pulses at 3 Hz. The release of tritiated NE was measured upon addition of increasing concentrations of unlabeled NE to exogenously activate the inhibitory ␣ 2 -autoreceptor. Although neither basal nor stimulated NE release differed between the groups, significantly lower pIC 50 and I max estimates of the concentration-response curves of exogenous NE on [ 3 H]NE release were observed in CRF rats, suggesting a diminished autoinhibition of hypothalamic noradrenergic terminals in CRF. Western blotting of tissue homogenates disclosed a significantly reduced abundance of ␣ 2 -autoreceptor protein in hypothalamic tissue from CRF rats. These abnormalities were selectively observed in the hypothalamus, whereas noradrenergic autoinhibition seemed unaltered in the hippocampus. The results suggest a diminished autoinhibition of hypothalamic NE release in CRF. Although impaired hypothalamic NE autoinhibition does not explain reduced GnRH secretion in CRF, it may be involved in the pathogenesis of sympathetic hyperactivity associated with this condition. D isorders of the reproductive system, clinically manifesting by impaired libido and fertility in adults and delayed or arrested puberty in adolescents, are common in chronic renal failure (CRF) (1). We and others previously demonstrated defective neuroendocrine activation of the gonadotropic hormone axis both in patients with CRF and in experimental uremia, with evidence for reduced pulsatile release of gonadotropin releasing hormone (GnRH) from the mediobasal hypothalamus (2-5). Experimental findings suggest that uremia may influence the function of hypothalamic neurons by various mechanisms. We observed abnormal extracellular amino acid neurotransmitter concentrations in the mediobasal hypothalamus of uremic rats, compatible with disturbed regulation of hypothalamic neurons by higher neuronal centers (6). The function of brain synaptosomes is altered in experimental uremia (7-10). However, we also demonstrated direct inhibition of GnRH secretion from cultured hypothalamic neurons by a factor circulating in uremic serum (11).Norepinephrinergic axon terminals are located in proximity of GnRH cells in the anterior hypothalamus (12). Norepinephrine (NE) is able to stimulate GnRH release from the hypothalamus in a concentration-dependent manner in vitro ...

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Abnormal sodium transport in synaptosomes from brain of uremic rats.

Cited by 48 publications

References 40 publications

Taurine and Osmoregulation. IV. Cerebral Taurine Transport Is Increased in Rats with Hypernatremic Dehydration

Taurine and Osmoregulation. IV. Cerebral Taurine Transport Is Increased in Rats with Hypernatremic Dehydration

Abnormal cation transport in uremia. Mechanisms in adipocytes and skeletal muscle from uremic rats.

Impaired Autofeedback Regulation of Hypothalamic Norepinephrine Release in Experimental Uremia

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