Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potent diuretic and natriuretic properties of atrial natriuretic factor (ANF) suggest that atrial hormones may participate to the regulation of salt and water excretion under physiological conditions. ANF, via the increase of its intracellular second messenger cGMP, has been recently shown to inhibit the apical sodium channel of the inner medullary collecting tubule (IMCD). In addition, ANF inhibits renin and aldosterone synthesis and antagonizes the antinatriuretic effects of angiotensin II. ANF may also contribute to the excretion of free water by inhibiting both the secretion of vasopressin and its antidiuretic action. ANF appears to play an important physiological role in sodium repleted states, or when the effective plasma volume is increased. On the contrary, when the effective plasma volume is decreased or in sodium depleted states, the natriuretic effect of both endogenous and exogenous ANF is severely blunted. That ANF-resistance may be related to the activation of the renin-angiotensin-aldosterone axis, increased circulating catecholamines, renal sympathetic nerve stimulation, changes in renal hemodynamics or increased degradation of ANF. All these factors could explain the lack of significant natriuretic effect of both endogenous and exogenous ANF in some pathological conditions such as heart failure or liver cirrhosis. ANF may also been concerned in water homeostasis. In addition to the well-known osmoregulatory pathways of water metabolism, we recently found that ANF could be involved in the volume adjustment to acute water intake in normal man.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atrial natriuretic factor and the endocrine control of electrolyte homeostasis. 183 42

The mechanism of transepithelial NaCl transport was investigated in isolated perfused cortical collecting ducts from the kidneys of deoxycorticosterone-treated rats. In the presence of vasopressin, hydrochlorothiazide (0.1 mM) markedly reduced the net rate of Na absorption, Cl absorption, and active fluid absorption but did not significantly change the transepithelial voltage. Similarly, in the absence of vasopressin, hydrochlorothiazide decreased the rate of sodium absorption by 50% without affecting transepithelial voltage. Amiloride (30 microM) completely eliminated the lumen-negative voltage but decreased net sodium absorption only by approximately 50%. In the presence of amiloride, chloride absorption occurred against an electrochemical gradient for chloride, indicating that there was active chloride absorption. Bumetanide (0.1 mM) did not affect chloride absorption or spontaneous fluid absorption in the presence of vasopressin. The combination of amiloride and hydrochlorothiazide inhibited net sodium absorption by a greater extent than did either agent alone. These results demonstrate the presence of the following two parallel sodium transport pathways in cortical collecting ducts from mineralocorticoid-replete rats: 1) an electrogenic pathway blocked by amiloride, which presumably involves an apical sodium channel, and 2) a thiazide-inhibitable electroneutral pathway, which presumably utilizes apical Na-Cl cotransport and mediates secondary active transport of chloride.
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PMID:Thiazide-sensitive NaCl absorption in rat cortical collecting duct. 239 77

Phenamil, an analog of amiloride, has previously been shown to bind specifically to sodium channels in toad bladder (J.L. Garvin et al., J. Membrane Biol. 87:45-54, 1985). In this paper, 3H-phenamil was used to measure sodium channel density in both isolated epithelial cells and intact bladders. From the specific binding to intact bladders, a channel density of 455 +/- 102 channels/micron2 was calculated. No correlation between specific binding and the magnitude of irreversible inhibition of short-circuit current was found. Pretreatment of intact bladders with 1 mg/ml trypsin reduced specific binding to isolated cells by 82 +/- 5%. In isolated cells, neither aldosterone nor vasopressin had any significant effect on specific phenamil binding. It is inferred that phenamil binds to both open and closed channels which may be either in the mucosal membrane or in the submembrane space. Finally, and rather surprisingly, we found that 3H-phenamil binds irreversibly to the basolateral membrane at concentrations as low as 4 X 10(-7) M. Therefore, care must be used in interpreting binding studies with amiloride or its analog at such concentrations.
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PMID:Binding of 3H-phenamil, an irreversible amiloride analog, to toad urinary bladder: effects of aldosterone and vasopressin. 242 92

Isolated rat paraventricular (PVN) and supraoptic (SON) nuclei were perifused in vitro and oxytocin and vasopressin releases were measured by radioimmunoassay during rest and during electrical stimulation. Stimulations at a frequency of 10 Hz (10-s bursts, every 10 s for 5 min) and an intensity of 4 mA, induced significant hormone release only with long duration pulses (10 ms). Short pulses (1 ms) applied at various frequencies (10, 20, 40 or 80 Hz) and intensities (4, 5, 10 or 20 mA) had no effect. The electrically evoked release of both hormones was not affected by tetrodotoxin (TTX), a sodium channel blocker, but was blocked in low-calcium medium or in the presence of gallopamil hydrochloride (D-600), a calcium channel blocker. These results suggest that, following electrical stimulation, oxytocin and vasopressin are released locally within the magnocellular nuclei even when blocking action potentials. The possibility of dendritic release is discussed.
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PMID:Electrical stimulations of perifused magnocellular nuclei in vitro elicit Ca2+-dependent, tetrodotoxin-insensitive release of oxytocin and vasopressin. 243 5

Anatagonists to angiotensin, catecholamines, aldosterone, and vasopressin have long been used to help determine agonist roles in hypertension. We here call attention to a possible extension of this approach to detect, evaluate, and treat vascular sodium transport defects in hypertension. Two basic types of transport defects have been identified in the blood vessels of hypertensive animals, increased sodium permeability and decreased sodium pump activity. Intravenous injection of 6-iodo-amiloride, a sodium channel blocker and vasodilator, produces an immediate and sustained decrease in blood pressure in two genetic models of hypertension characterized by increased permeability of the vascular smooth muscle cell membrane to sodium (Okamoto spontaneously hypertensive rat, Dahl salt sensitive rat), whereas it produces only a transient fall in arterial pressure in two renal models of hypertension having normal sodium permeability in vascular smooth muscle cells (reduced renal mass-saline rat, one-kidney, one clip rat). Canrenone, a metabolic product of spironolactone which can compete with oubain for binding to Na+,K+-ATPase at the digitalis receptor site, decreases blood pressure in a low renin, volume expanded model of hypertension which has been shown to have depressed sodium pump activity in arteries and increased sodium pump inhibitor in plasma (reduced renal mass-saline rat) but has no effect on blood pressure in a genetic model of hypertension which has been shown to have increased sodium pump activity secondary to increased sodium permeability (spontaneously hypertensive rat). Thus, a sodium channel blocker and a competitor to ouabain binding can detect and determine the functional significance of sodium transport defects in the blood vessels of intact hypertensive animals. Studies in red and white blood cells suggest that similar defects may exist in the blood vessels of hypertensive humans. Thus, this approach, probing for vascular transport defects in the intact animal, may ultimately also be useful in the clinical setting.
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PMID:Pharmacologic agents for the in vivo detection of vascular sodium transport defects in hypertension. 244 62

Studies of the molecular nature of epithelial sodium channels are in their infancy and have largely involved experiments in which the interaction between amiloride and this transport process has been examined. Because of the inherent geometric complexity of epithelial tissues, these studies have in large measure been macroscopic in nature, with the molecular details of transport being deduced. In the past five years, however, the molecular biology of these critical ion channels has been studied directly. The development of radioactive high-affinity probes, the application of patch-clamp and reconstitution techniques, the generation of specific antibodies, and the formulation of epithelial cDNA expression libraries have propelled the field of epithelial ion channels into a new era. Now, for the first time, we can rigorously address questions concerning the molecular nature of the amiloride block, the channel's selectivity to alkali metal cations, and the modulation of ion transport through this channel by other ions (such as calcium), hormones (such as vasopressin, aldosterone, and atrial natriuretic factor), or intracellular second messengers (such as cAMP or cGMP). The complexity of the epithelial sodium channel's structure may reflect the constitutive and regulatory role this protein plays in sodium homeostasis. The epithelial sodium channel is continually operating, constantly changing its activity on a second-to-second basis. Hence, its tonic functions are probably modulated by a myriad of factors, most of which are unknown. With the application of molecular techniques, a much clearer understanding of the nature and regulation of epithelial sodium channel processes in health and disease will emerge in the years to come.
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PMID:The biology of amiloride-sensitive sodium channels. 246 56

Endothelins modulate not only vasoregulation but also neurotransmission and hormone secretion, specifically vasopressin (AVP) secretion. The present studies were designed to ascertain the site of action and the participation of membrane cation channels mediating endothelin-3-induced AVP release. Experiments were performed using standard and compartmentalized hypothalamo-neurohypophysial explants. The stimulatory action of endothelin-3 on AVP release occurred at the neural lobe, consistent with the failure of sodium channel blockade to decrease AVP secretion. Calcium channel antagonism or chelation of extracellular calcium inhibited neurohormone release, but blockade of calcium mobilization from intracellular stores with 8-(diethyl-amino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) did not. Inhibition of the calcium-activated potassium channel with charybdotoxin increased AVP levels dose dependently. Potassium ionophore abolished this response, as did TMB-8, but inhibition of calcium entry failed to do so. A subthreshold dose of charybdotoxin potentiated AVP secretion to submaximal stimulation with endothelin-3 that was prevented only by concomitant blockade of calcium influx and intracellular mobilization. The data support interaction between calcium and potassium channels at the secretory terminal. Collectively, these data are consistent with endothelin-3 receptor activation at the secretory terminal initiating calcium entry, thereby leading to depolarization independent of sodium conductances. This mechanism is opposed by hyperpolarizing forces linked to calcium accumulation, namely, the charybdotoxin-sensitive calcium-activate potassium channel. Interaction of the depolarizing and repolarizing systems enables grade AVP secretion from the neural lobe. These findings do not preclude the participation of other systems as well.
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PMID:Cation channel mechanisms in ET-3-induced vasopressin secretion by rat hypothalamo-neurohypophysial explants. 753 90

Although prevention of heart failure recently has become a realistic issue, management of heart failure once the syndrome has developed, is mainly supportive, based on the various cardiac and peripheral changes which occur in the course of heart failure. Of these, abnormal neurohormonal activation is of major pathophysiologic and prognostic significance. Consequently, modulation of neuroendocrine activation is now recognized a prime target in the treatment of heart failure, besides diuretic therapy. In this respect, the value of converting enzyme inhibition is well established. Future developments in this area include dopaminergic agents, vasopressin antagonists, angiotensin II receptor antagonists, renin inhibitors, spironolactone and, possibly, ANF peptidase inhibitors. Besides diuretics, necessary when signs of fluid retention are present, the approach to heart failure management involves other pharmacologic issues. In view of abnormal vascular control with vasoconstriction prevailing during progressive heart failure, it clearly makes sense to vasodilate. However, of available vasodilators, only the combination of relatively high dose nitrates and hydralazine has proven to be of clinical significance, in terms of hemodynamics, exercise capacity and survival. It is possible, though, that novel generation dihydropyridine derivatives may prove beneficial as well. Thus far, there has been much debate concerning the usefulness and particularly the safety of positive inotrope therapy and inodilator treatment. Taken together, this concern relates to presence and predominance of cAMP-dependent mechanisms to induce these effects. Thus, sympathomimetic agents and phosphodiesterase inhibitors, such as milrinone or enoximone, are without beneficial effects, but instead shorten survival during long-term therapy. This may be different where compounds which act through cAMP-independent mechanisms, i.e., calcium sensitization or sodium channel stimulation, are concerned, but needs to be confirmed yet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Congestive heart failure. Drug therapy: central or peripheral approach? 791 52

The amiloride-sensitive epithelial sodium channel constitutes the rate-limiting step for sodium reabsorption in epithelial cells that line the distal part of the renal tubule, the distal colon, the duct of several exocrine glands, and the lung. The activity of this channel is upregulated by vasopressin and aldosterone, hormones involved in the maintenance of sodium balance, blood volume and blood pressure. We have identified the primary structure of the alpha-subunit of the rat epithelial sodium channel by expression cloning in Xenopus laevis oocytes. An identical subunit has recently been reported. Here we identify two other subunits (beta and gamma) by functional complementation of the alpha-subunit of the rat epithelial Na+ channel. The ion-selective permeability, the gating properties and the pharmacological profile of the channel formed by coexpressing the three subunits in oocytes are similar to that of the native channel.
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PMID:Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. 750 38

The epithelial amiloride-sensitive sodium channel constitutes the rate limiting step for sodium reabsorbtion by the epithelial lining the distal part of the kidney tubule, the urinary bladder and the distal colon. Reabsorbtion of sodium through this channel, which is regulated by hormones such as aldosterone and vasopressin, is one of the essential mechanisms involved in the regulation of sodium balance, blood volume and blood pressure. Here we isolate a DNA from epithelial cells of rat distal colon and identify it by functional expression of an amiloride-sensitive sodium current in Xenopus oocyte. The deduced polypeptide (698 amino acids) has at least two putative transmembrane segments. Expression of this protein in Xenopus oocytes reconstitutes the functional properties of the highly selective amiloride-sensitive, epithelial sodium channel. The gene encoding this rat sodium channel subunit shares significant sequence similarity with mec-4 and deg-1, members of a family of Caenorhabditis elegans genes involved in sensory touch transduction and, when mutated, neuronal degeneration. We propose that the gene products of these three genes are members of a gene family coding for cation channels.
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PMID:Epithelial sodium channel related to proteins involved in neurodegeneration. 842 2


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