title: Stimulation of NHE3 in OKP cells by an autocrine mechanism.
abstract: OBJECTIVE
  Chronic hypokalemia increases NHE3 activity in OKP cells. The aim of the present study was to determine whether an autocrine mechanism is involved in this activation.
  
  
  METHODS
  After incubation of OKP cells in normal-K(+) and low-K(+) media for 24 h, the potassium concentration in the low-K(+) media was adjusted to a normal level. These conditioned media were then used as the normal-K(+) and low-K(+) supernatants. Other OKP cells were incubated in these normal-K(+) and low-K(+) supernatants and the mechanism of Na(+)/H(+) antiporter activation was examined.
  
  
  RESULTS
  The EIPA-resistant Na(+)/H(+) antiporter activity of OKP cells increased after 4 h incubation in the low-K(+) supernatant, and the amount of NHE3 protein increased at 24 h. Since both BQ788 and saralasin blocked this antiporter activation, the supernatant concentration of endothelin I (ET-I) and angiotensin II (Ang-II) were measured. The ET-I concentration was reduced, but the Ang-II concentration remained unchanged. There was a significant association between a reduction in the ET-I concentration and an increase in Na(+)/H(+) antiporter activity, but only when Ang-II was present in the supernatant.
  
  
  CONCLUSIONS
  An autocrine mechanism is involved in the activation of NHE3 in OKP cells. Both ET-I and Ang-II play a role in this activation.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Jichi Omiya Medical Center, Jichi Medical School, Saitama-shi, Saitama-Ken, Japan. morimasa@jichi.ac.jp
authors.forename: Morimasa
authors.initials: M
authors.lastname: Amemiya
authors.forename: Honami
authors.initials: H
authors.lastname: Mori
authors.forename: Shigeki
authors.initials: S
authors.lastname: Imamura
authors.forename: Akira
authors.initials: A
authors.lastname: Toyoda
authors.forename: Izumi
authors.initials: I
authors.lastname: Funayama
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Asano
authors.forename: Eiji
authors.initials: E
authors.lastname: Kusano
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tabei
mesh_terms: D000138:Acidosis / Q000201:enzymology / Q000378:metabolism; D000584:Amiloride / Q000031:analogs & derivatives*; D000804:Angiotensin II / Q000378:metabolism / Q000502:physiology; D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D016227:Benzoquinones; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D047029:Lactams, Macrocyclic; D009842:Oligopeptides / Q000494:pharmacology; D009893:Opossums; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology; D044023:Receptor, Endothelin B / Q000502:physiology; D017828:Rifabutin / Q000031:analogs & derivatives; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors
chemical_list: D016227:Benzoquinones; D017077:Culture Media, Conditioned; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D047029:Lactams, Macrocyclic; D009842:Oligopeptides; D010880:Piperidines; D011809:Quinones; D044023:Receptor, Endothelin B; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II; D017828:Rifabutin; C086539:BQ 788; C020754:herbimycin; D000584:Amiloride; D011505:Protein-Tyrosine Kinases; D011188:Potassium; C039614:ethylisopropylamiloride