Determination of CRF activity in rats treated with Monase, dexamethasone, and morphine

¹ Endocrine and Polypeptide Laboratories, Veterans Administration Hospital, and Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana

The effects of Monase (3-(2-aminobutyl)-indole acetate) on adrenocortical function were studied in rats with the aim of developing a new assay for corticotropin-releasing (CRF) activity. Administration of Monase and Nembutal led, after a 3-hr period, to inhibition of the increase in plasma levels of corticosterone which normally follows the stress of injection into jugular vein and laparotomy. Monase does not interfere with formation and secretion of corticosterone, but acts by suppressing secretion of ACTH. Monase inhibited the increased corticosterone secretion normally produced by administration of 5–15 mU of lysine vasopressin, 50 µg histamine, and 5 µg epinephrine, but did not block the response to 500 µg histamine or 30 mU vasopressin. Peptides such as lysine and arginine vasopressin, "natural" dimer of lysine vasopressin, angiotensin II, and ₁- and ß-CRF were tested at several dose levels in groups of rats treated with morphine-Nembutal, dexamethasone-Nembutal, or Monase-Nembutal, and the responses are reported.

Key Words: corticotropin-releasing factor (CRF) • neuroendocrine-blocking agents • blocking action of Monase on endogenous ACTH in rats • dexamethasone or morphine-Nembutal blockade • comparison of ACTH-releasing activity of vasopressin, angiotensin II, and CRF

Submitted on November 19, 1964