Connexin 37 contributes to water homeostasis and urinary concentrating ability

The kidney is the main organ regulating composition of body fluids. A considerable number of hormones control the activity of renal cells to maintain hydromineral equilibrium. It becomes more and more difficult to interpret this multihormonal control in terms of regulatory processes. To illustrate this complexity, the hormonal regulation of electrolyte transport in the nephron thick ascending limb is taken as an example. This nephron segment is largely responsible for two kidney functions: the urinary-concentrating ability (by its capacity to deliver hypertonic sodium chloride into the medullary interstitium) and regulation of magnesium excretion into final urine. Six hormones are presently identified as acting on the transport of both sodium chloride and magnesium ions in this nephron segment. Therefore, the pertinent question is how the thick ascending limb and, hence, the kidney, is capable of regulating water balance independently from magnesium balance. It is proposed that the hormones act in combination: circulating levels of the individual hormones acting on these cells may determine the configuration of the paracellular and transcellular transport pathways of the epithelium either in the “sodium” or “magnesium” mode. The configuration would depend on the distribution and activity of the receptor at the surface of the basolateral membrane in contact with the circulating hormones. This distribution along with stimulation of respective signal transduction pathways would lead to the final biological effects. It is already known that the distribution of cell receptors may vary according to factors such as age, nutritional variability, hormonal status, degree of desensitization of the receptors, etc. The modulation of hormonal responses would depend therefore on the degree of coupling of hormone-receptor complexes to different intracellular transduction pathways and on the resulting negative and/or positive interactions between these pathways.

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Vasopressin-vermittelte Wasserrückresorption im Sammelrohr der Niere

BIOspektrum ◽

10.1007/s12268-021-1544-1 ◽

2021 ◽

Vol 27 (2) ◽

pp. 165-167

Author(s):

Sandrine Baltzer ◽

Enno Klussmann

Keyword(s):

Water Balance ◽

Small Molecules ◽

High Throughput ◽

Molecular Mechanisms ◽

Collecting Duct ◽

Water Channel ◽

Water Reabsorption ◽

Balance Disorders ◽

Water Homeostasis ◽

Balance Disorder

AbstractVasopressin-mediated water reabsorption from primary urine in the renal collecting duct is essential for regulating body water homeostasis and depends on the water channel aquaporin-2 (AQP2).Dysregulation of the process can cause water balance disorders. Here, we present cell-based high-throughput screenings to identify proteins and small molecules as tools to elucidate molecular mechanisms underlying the AQP2 control and as potential starting points for the development of water balance disorder drugs.

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Interactions between ADH and prostaglandins in isolated erythrocyte-perfused rat kidney

AJP Renal Physiology ◽

10.1152/ajprenal.1987.252.2.f331 ◽

1987 ◽

Vol 252 (2) ◽

pp. F331-F337 ◽

Cited By ~ 7

Author(s):

W. Lieberthal ◽

M. L. Vasilevsky ◽

C. R. Valeri ◽

N. G. Levinsky

Keyword(s):

Sodium Excretion ◽

Rat Kidney ◽

Urine Osmolality ◽

Sodium Reabsorption ◽

Urinary Osmolality ◽

Hemodynamic Characteristics ◽

Urinary Concentrating Ability ◽

Tubular Morphology ◽

Isolated Kidneys

Interactions between antidiuretic hormone (ADH) and renal prostaglandins in the regulation of sodium reabsorption and urinary concentrating ability were studied in isolated erythrocyte-perfused rat kidneys (IEPK). In this model, hemodynamic characteristics are comparable to those found in vivo, and tubular morphology is preserved throughout the period of perfusion. [Deamino]-D-arginine vasopressin (dDAVP) markedly reduced fractional sodium excretion (FE Na) in the IEPK from 3.5 +/- 0.6 to 0.45 +/- 0.14%. After indomethacin, FE Na fell still further to 0.08 +/- 0.02%. In the absence of dDAVP indomethacin had no effect on sodium excretion; FE Na was 2.4 +/- 0.6% in control and 2.0 +/- 0.4% in indomethacin-treated groups. dDAVP increased urine osmolality in the IEPK to 741 +/- 26 mosmol/kg. When prostaglandin synthesis was blocked with indomethacin, urinary osmolality increased further to 1,180 +/- 94 mosmol/kg. In isolated kidneys perfused without erythrocytes (IPK), dDAVP decreased FENa from 14.5 +/- 1.8% to 9.6 +/- 1.2%; addition of indomethacin had no further effect. dDAVP increased urine osmolality only modestly to 350 +/- 12 mosmol/kg in the IPK and indomethacin did not increase concentrating ability further (342 +/- 7 mosmol/kg). Thus the IEPK (unlike the IPK) can excrete a markedly hypertonic urine in response to ADH. ADH also enhances tubular reabsorption of sodium in the IEPK. Prostaglandins inhibit both these actions of ADH but do not directly affect sodium excretion in the absence of the hormone.

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Astrocyte Glutamate Uptake and Water Homeostasis Are Dysregulated in the Hippocampus of Multiple Sclerosis Patients With Seizures

ASN NEURO ◽

10.1177/1759091420979604 ◽

2020 ◽

Vol 12 ◽

pp. 175909142097960

Author(s):

Andrew S. Lapato ◽

Sarah M. Thompson ◽

Karen Parra ◽

Seema K. Tiwari-Woodruff

Keyword(s):

Multiple Sclerosis ◽

Mouse Model ◽

Regional Differences ◽

Neuronal Excitability ◽

Demyelinating Disease ◽

Glutamate Uptake ◽

Cx43 Expression ◽

Water Homeostasis ◽

Hippocampal Astrocytes ◽

Multiple Sclerosis Patients

While seizure disorders are more prevalent among multiple sclerosis (MS) patients than the population overall and prognosticate earlier death & disability, their etiology remains unclear. Translational data indicate perturbed expression of astrocytic molecules contributing to homeostatic neuronal excitability, including water channels (AQP4) and synaptic glutamate transporters (EAAT2), in a mouse model of MS with seizures (MS+S). However, astrocytes in MS+S have not been examined. To assess the translational relevance of astrocyte dysfunction observed in a mouse model of MS+S, demyelinated lesion burden, astrogliosis, and astrocytic biomarkers (AQP4/EAAT2/ connexin-CX43) were evaluated by immunohistochemistry in postmortem hippocampi from MS & MS+S donors. Lesion burden was comparable in MS & MS+S cohorts, but astrogliosis was elevated in MS+S CA1 with a concomitant decrease in EAAT2 signal intensity. AQP4 signal declined in MS+S CA1 & CA3 with a loss of perivascular AQP4 in CA1. CX43 expression was increased in CA3. Together, these data suggest that hippocampal astrocytes from MS+S patients display regional differences in expression of molecules associated with glutamate buffering and water homeostasis that could exacerbate neuronal hyperexcitability. Importantly, mislocalization of CA1 perivascular AQP4 seen in MS+S is analogous to epileptic hippocampi without a history of MS, suggesting convergent pathophysiology. Furthermore, as neuropathology was concentrated in MS+S CA1, future study is warranted to determine the pathophysiology driving regional differences in glial function in the context of seizures during demyelinating disease.

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