TY - JOUR
T1 - Functional role of histamine receptors in the renal cortical collecting duct cells
AU - Sudarikova, Anastasia V.
AU - Fomin, Mikhail V.
AU - Sultanova, Regina F.
AU - Zhao, Ying
AU - Perez, Samantha
AU - Domondon, Mark
AU - Shamatova, Margarita
AU - Lysikova, Daria V.
AU - Spires, Denisha R.
AU - Ilatovskaya, Daria V.
N1 - Funding Information:
This study was supported by National Heart, Lung, and Blood Institute (NHLBI) Grants R01 HL148114 (to D.V.I.), NHLBI R01HL148114-02S1 (to D.V.I. and D.R.S.), the Augusta University, Department of Physiology startup funds (to D.V.I.), and the AHA Postdoctoral Fellowship (to D.R.S.).
Publisher Copyright:
© 2022 the American Physiological Society.
PY - 2022/4
Y1 - 2022/4
N2 - Histamine is an important immunomodulator, as well as a regulator of allergic inflammation, gastric acid secretion, and neurotransmission. Although substantial histamine level has been reported in the kidney, renal pathological and physiological effects of this compound have not been clearly defined. The goal of this study was to provide insight into the role of histamine-related pathways in the kidney, with emphasis on the collecting duct (CD), a distal part of the nephron important for the regulation of blood pressure. We report that all four histamine receptors (HRs) as well as enzymes responsible for histamine metabolism and synthesis are expressed in cultured mouse mpkCCDcl4 cells, and histamine evokes a dose-dependent transient increase in intracellular Ca2 in these cells. Furthermore, we observed a dose-dependent increase in cAMP in the CD cells in response to histamine. Short-circuit current studies aimed at measuring Na reabsorption via ENaC (epithelial Na channel) demonstrated inhibition of ENaC-mediated currents by histamine after a 4-h incubation, and single-channel patch-clamp analysis revealed similar ENaC open probability before and after acute histamine application. The long-term (4 h) effect on ENaC was corroborated in immunocytochemistry and qPCR, which showed a decrease in protein and gene expression for aENaC upon histamine treatment. In summary, our data highlight the functional importance of HRs in the CD cells and suggest potential implications of histamine in inflammation-related renal conditions. Further research is required to discern the molecular pathways downstream of HRs and assess the role of specific receptors in renal pathophysiology.
AB - Histamine is an important immunomodulator, as well as a regulator of allergic inflammation, gastric acid secretion, and neurotransmission. Although substantial histamine level has been reported in the kidney, renal pathological and physiological effects of this compound have not been clearly defined. The goal of this study was to provide insight into the role of histamine-related pathways in the kidney, with emphasis on the collecting duct (CD), a distal part of the nephron important for the regulation of blood pressure. We report that all four histamine receptors (HRs) as well as enzymes responsible for histamine metabolism and synthesis are expressed in cultured mouse mpkCCDcl4 cells, and histamine evokes a dose-dependent transient increase in intracellular Ca2 in these cells. Furthermore, we observed a dose-dependent increase in cAMP in the CD cells in response to histamine. Short-circuit current studies aimed at measuring Na reabsorption via ENaC (epithelial Na channel) demonstrated inhibition of ENaC-mediated currents by histamine after a 4-h incubation, and single-channel patch-clamp analysis revealed similar ENaC open probability before and after acute histamine application. The long-term (4 h) effect on ENaC was corroborated in immunocytochemistry and qPCR, which showed a decrease in protein and gene expression for aENaC upon histamine treatment. In summary, our data highlight the functional importance of HRs in the CD cells and suggest potential implications of histamine in inflammation-related renal conditions. Further research is required to discern the molecular pathways downstream of HRs and assess the role of specific receptors in renal pathophysiology.
KW - collecting duct
KW - epithelial Na channels
KW - histamine
KW - histamine receptors
KW - kidney
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U2 - 10.1152/ajpcell.00420.2021
DO - 10.1152/ajpcell.00420.2021
M3 - Article
C2 - 35081320
AN - SCOPUS:85128245196
SN - 0363-6143
VL - 322
SP - C775-C786
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 4
ER -