Abstract
Arginine vasopressin (Avp) is a conserved pleiotropic hormone that is known to regulate both water reabsorption and ion balance; however, many of the mechanisms underlying its effects remain unclear. Here, we used zebrafish embryos to investigate how Avp modulates ion and acid–base homeostasis. After incubating embryos in double-deionized water for 24 h, avp mRNA expression levels were significantly upregulated. Knockdown of Avp protein expression by an antisense morpholino oligonucleotide (MO) reduced the expression of ionocyte-related genes and downregulated whole-body Cl− content and H+ secretion, while Na+ and Ca2+ levels were not affected. Incubation of Avp antagonist SR49059 also downregulated the mRNA expression of sodium chloride cotransporter 2b (ncc2b), which is a transporter responsible for Cl− uptake. Correspondingly, avp morphants showed lower NCC and H+-ATPase rich (HR) cell numbers, but Na+/K+-ATPase rich (NaR) cell numbers remained unchanged. avp MO also downregulated the numbers of foxi3a- and p63-expressing cells. Finally, the mRNA expression levels of calcitonin gene-related peptide (cgrp) and its receptor, calcitonin receptor-like 1 (crlr1), were downregulated in avp morphants, suggesting that Avp might affect Cgrp and Crlr1 for modulating Cl− balance. Together, our results reveal a molecular/cellular pathway through which Avp regulates ion and acid–base balance, providing new insights into its function.
Highlights
Arginine vasopressin (Avp), sometimes called antidiuretic hormone, is synthesized by neurons in the mammalian anterior hypothalamus that project to the posterior pituitary
Sci. 2020, 21, 3957 and NM_001110125, respectively) was examined in various tissues by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), using rpl13a as an internal control. avp mRNA was abundantly expressed in brain, muscle, heart, kidney, and gill, and it was moderately expressed in eye, liver, and intestine (Figure 1a)
Our study shows that Avp participates in ion regulation and is especially important for Cl− balance and acid/base balance
Summary
Arginine vasopressin (Avp), sometimes called antidiuretic hormone, is synthesized by neurons in the mammalian anterior hypothalamus that project to the posterior pituitary. Avp is released from the posterior pituitary and enters the circulatory system [1]. Previous studies suggested that AVP participates in cation transport in the renal tubules, regulating the reabsorption of Na+, Mg2+, and Ca2+, as well as the secretion of K+ in the distal segment of the nephron; it modulates intracellular pH in the collecting duct cells [2,3,4]. Avp regulates NaCl reabsorption by phosphorylating the Na+-K+-2Cl−. Cotransporter (Nkcc2) and Na+-Cl− cotransporter (Ncc) in the thick ascending limb of Henle’s loop and distal convoluted tubule, respectively [7]. Injection of synthetic Avp (deamino-Cys-1, d-Arg-8 vasopressin, dDAVP) into Avp-deficient transgenic rats was able to stimulate Ncc phosphorylation, which led to translocation of Ncc to the apical membrane [8]
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