Inhibition of Pineal Type‐II 5′‐Deiodinase Does Not Affect the Nocturnal Increase of N‐Acetyltransferase Activity and Melatonin Content in Either Euthyroid or Thyroidectomized Rats

1区 · 医学

Article

作者: Juan M. Guerrero ; Russel J. Reiter ; Armando Menendez-Pelaez ; Manuel Puig-Domingo ; Celsa Santana

The presence of type‐II thyroxine 5′‐deiodinase (5′‐D) activity in rat pineal gland has been previously described. In the present paper, 5′‐D activity, N‐acetyltransferase (NAT) activity, and melatonin content were measured in the same rat pineal. Each of these constituents exhibits a nocturnal increase with peak values at 0100 h for melatonin (1.20 ± 0.12 ng/gland) and at 0300 h for both 5′‐D (39.5 ± 11.9 fmol/gland/h) and NAT (8.38 ± 1.04 nmol/gland/h) activities. In vivo treatment with iopanoic acid (IOP) completely prevented the nocturnal increase in 5′‐D activity (14.1 ± 2.6 fml/gland/h at 0300 h) with no modification in either the NAT activity or melatonin content. Thyroidectomy greatly enhanced the 5′‐D activity during the dark period (102.9 ± 10.2 vs. 31.6 ± 4.2 fmol/gland/h), reaching a peak at 0200 h; thyroidectomy, however, did not affect daytime pineal 5′‐D activity (3.11 ± 0.78 vs. 2.5 + 0.92 fmol/gland/h). Treatment of rats with IOP acid completely inhibited the pineal 5′‐D activity in both control (7.86 ± 0.88 fmol/gland/h) and thyroidectomized animals (2.24 ± 1.10 fmol/gland/h) with no change in the melatonin content of the gland (1.21 ± 0.32 vs. 0.99 ± 0.18 ng/gland).

1983-09-01·Experimental Biology and Medicine

Uptake of lopanoic Acid and Its Glucuronide Conjugate by Rat Hepatocytes in Primary Culture

Article

作者: James L. Barnhart ; Brenda L. Witt

Uptake of iopanoic acid (IOP) and iopanoate glucuronide (IOP-G) was studied in 3-day primary cultures of rat hepatocytes isolated by the collagenase perfusion method. 125I activity of cells after incubation with 125I-IOP (10-100 microM) and 125I-IOP-G (10-100 microM) was used as a measure of uptake. At each concentration, uptake was linear for the first 45 sec. In the absence of albumin, the initial uptake velocity was directly proportional to the concentration or IOP or IOP-G and was nonsaturable up to 100 microM. The calculated uptake rate constants for IOP and for IOP-G were 0.059 and 0.048 nmole/(mg protein X min X microM), respectively. IOP uptake was not inhibited by sodium taurocholate nor by the contrast agents iodipamide, ipodate, and iopronic acid. The data indicate that the enhancement of IOP excretion by bile salts noted in vivo does not occur at the uptake step and that the hepatic uptake of both IOP and IOP-G in the absence of albumin is limited by diffusion.

1980-09-01·Nihon yakurigaku zasshi. Folia pharmacologica Japonica

[Chemical structure biliary excretion of iodine-containing contrast agents in hemoglobin-free perfused rat liver and in vivo (author's transl)].

Article

作者: Oshino, N ; Azuma, H

Pharmacokinetical properties of eight triiodobenzene derivatives, X-ray contrast agents, were studied in the hemoglobin-free perfused rat liver with emphasis on the structural relation to biliary transport. With chemical modification of the basic structure, these agents showed different characteristics in the processes of diffusion into hepatocytes, accumulation in the cells and active transport into the bile, and were separated into four groups; [I]: Iotroxic acid (1), Iodipamic acid (2), Iodoxamic acid (3), and Ioglycamic acid (4) which showed faster rates of diffusion into hepatocytes [(1) greater than or equal to (2) greater than (3) greater (4)] and also of biliary excretion [(1) greater than (2) greater than (4) greater than (3)], [II]: Diatrizoic acid and Metrizamide showed poor diffusion and biliary excretion, [III]: Iopodic acid showed the highest permeability into and accumulation in hepatocytes with little biliary excretion, [IV]: ZK73 215 was slowly transported into the bile, yet, showed little permeation through the cell membrane. Characteristics of (1), (2) and (3) observed in the perfused liver were, in principle, confirmed in the pharmacokinetical profile observed in vivo. However, the fast diffusion of (2) into the hepatocytes appears to be hampered by high binding ability with serum proteins, whereas the relatively poor profile of the biliary excretion of (3) was improved by its low protein-binding in blood in vivo. Superiority of (1) as a cholangiographic agent was demonstrated by the fast biliary excretion in both the case of experimental systems and moderate protein-binding.

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