A POTENT NEW SYNTHETIC ANALOG OF VASOPRESSIN WITH RELATIVE AGONIST SPECIFICITY FOR THE PITUITARY

The data indicate that analogs of vasopressin can be synthesized which are relatively selective for agonist activity at pituitary vasoppressin receptors, and in doing so, further support the contention that the pituitsary receptor is quite distinct from the classical V1 receptor.

Abstract

The biological activity of a new synthetic analog of vasopressin, deamino[D-3-(3'-pyridyl)-Ala2, Arg8] vasopressin, was assessed in a number of assays. Antidiuretic (V2) and vasoconstrictor (V1), agonist and antagonist activities were assessed in rats in vivo. Corticotropin-releasing activity was assessed with cultured dissociated ovine anterior pituitary cells in vitro and in sheep in vivo. Compared to vasopressin, the analog is a weak agonist at antidiuretic receptors (1/381 compared to AVP); it is a weak antagonist of the vasoconstrictor response (pA2 = 6.22). Nonetheless, the analog is a full, relatively potent agonist at pituitary corticotrope receptors (relative potency of 1/36). These data indicate that analogs of vasopressin can be synthesized which are relatively selective for agonist activity at pituitary vasopressin receptors, and in doing so, further support the contention that the pituitary receptor is quite distinct from the classical V1 receptor.