Biochemical pharmacology
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Biochemical pharmacology · Feb 1994
Comparative StudyEffect of a new, potent, non-peptide V1a vasopressin antagonist, SR 49059, on the binding and the mitogenic activity of vasopressin on Swiss 3T3 cells.
The effects of SR 49059, a new non-peptide, selective arginine vasopressin (AVP), V1a antagonist, were investigated both on AVP's receptors and on the mitogenic effects of AVP on Swiss 3T3 fibroblasts. We characterized the AVP V1a receptors on Swiss 3T3 cell membranes using the new highly specific AVP V1a radioiodinated ligand, 125I-linear AVP antagonist. Specific binding of the 125I-linear AVP antagonist was saturable, time-dependent and reversible. ⋯ SR 49059 was even about six times more efficient than d(CH2)5Tyr(Me)AVP in inhibiting AVP-induced DNA synthesis. Moreover, SR 49059 fully inhibited Swiss 3T3 fibroblast proliferation since it completely blocked AVP-stimulated 3T3 cell growth from the G1/G0 into the S/G2M phase, as evidenced by cell cycle analysis using a cytofluorometer. In summary, SR 49059, through direct interaction at AVP V1a receptors, exerts the most potent antiproliferative effect yet described for any V1a antagonist on Swiss 3T3 cells.