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In vitro adrenocorticotropin/beta-endorphin-releasing activity of vasopressin analogs is related neither to pressor nor to antidiuretic activity.

The ability of vasopressin and related analogs to induce ACTH, beta-endorphin, and beta-lipotropin release was studied in vitro using incubated rat anterior pituitary quarters or a perifused rat isolated anterior pituitary cell column. Vasopressin and its analogs exhibited corticotropin-releasing factor (CRF)-like activity in a rank order which was different from those for vasopressor or antidiuretic activity. Two dissimilar antagonists with antivasopressor activity showed different effects: one possessed CRF-like activity itself, the other blocked the CRF-like activity of vasopressin. Another antagonist with antipressor and also antiantidiuretic activity had no effect when given alone and also didn't block the CRF-like activity of vasopressin. Some analogs were also tested for their effects on cAMP accumulation. Analogs, which possessed CRF-like activity or blocked CRF-like activity of vasopressin, stimulated cAMP accumulation or inhibited vasopressin-stimulated cAMP accumulation in anterior pituitary quarters, respectively. These results imply that the structural requirements of the CRF-like activity of vasopressin differ from those of the pressor and antidiuretic activity. Therefore, it is possible that the pituitary receptors responsible for CRF-like activity of vasopressin represent a separate category of vasopressin receptors which may be linked to an adenylate cyclase.