Amiloride inhibition of triiodothyronine stimulated hepatocyte proliferation in vivo, and involvement of the intracellular Na+ content in mitotic regulation: an X-ray microanalytic study.
Energy dispersive X-ray microanalysis was carried out on the nuclei of hepatocytes stimulated to proliferate by the injection of a pharmacological dose of triiodothyronine (T3). The Na+ content displayed a continuous time-dependent increase in T3 stimulated animals. The Cl- concentration followed the same pattern as did the sodium, but its increase was lower. In contrast to Na+ and Cl- concentrations, the alteration in K+ content displayed a slight but statistically significant decrease at 8 h and 16 h from T3 injection and returned to the control levels by 22 h. The modifications of the Na+ and K+ content of the nuclei are reflected in their Na+:K+ molar ratios. A positive correlation was found between the increase of this parameter and the DNA synthesis rate of T3 stimulated hepatocytes. Amiloride was able to inhibit the stimulatory effect of the hormone, blocking the increase of both the intranuclear Na+:K+ ratio and of the DNA synthesis rate of hepatocytes. The findings are consistent with the hypothesis that a high Na+ content is associated with mitogenesis and, moreover, that an increased Na+ influx plays a causal role in regulating cell proliferation.
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000502:physiology; D002712:Chlorides / Q000502:physiology; D004261:DNA Replication; D004577:Electron Probe Microanalysis; D005260:Female; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008938:Mitosis; D011188:Potassium / Q000502:physiology; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000502:physiology*; D014284:Triiodothyronine / Q000037:antagonists & inhibitors*
D002712:Chlorides; D011719:Pyrazines; D014284:Triiodothyronine; D000584:Amiloride; D012964:Sodium; D011188:Potassium