Effects of ACTH and its Synthetic Analogues on Water Balance in Rats

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Abstract

Effects of native ACTH and various synthetic ACTH analogues on water balance alcohol-anesthesized polyuria rats were examined. Purified porcine ACTH had an apparent anti-diuretic action on the rats. Synthetic ACTH peptides consisting of 27, 24, 17, and 16 amino acids were biphasic, initially diuretic then anti-diuretic, and the peptides having 14, 13, and 10 amino acids were only diuretic. Small ACTH fragments consisting of 8, 6, 5, and 4 amino acids were inactive in the doses so far examined. In analogues consisting of 18 amino acids, replacement of N-terminal amino acid with β-alanine orα-aminoisobutyric acid (Ibu) and protection of the C-terminal carboxyl group by amide formation enhanced the anti-diuretic action. Purified TSH, LH, FSH, and prolactin probably inert under the experimental condition. Similar biphasic effect of the Ibu1-ACTH (1-18)-amide was also observed in hypophysectomized or adrenalectomized rats with almost the same potency as that in nonoperated rats. Weak diuretic action of Ibu1-ACTH (1-18)-amide was also demonstrated in water-loaded intact rats.

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