Vasopressin induces selective desensitization of its mitogenic response in Swiss 3T3 cells

Abstract

Prior incubation of quiescent cultures of Swiss 3T3 cells with vasopressin leads to loss of mitogenic stimulation on its subsequent addition in the presence of a synergistic growth factor. This desensitization is selective for vasopressin, requires prolonged incubation (half-maximal desensitization after 12 hr of treatment) for its induction, and is reversed after a 48-hr incubation in the absence of vasopressin. It is elicited by concentrations of vasopressin, and several analogues, similar to those required for stimulation of DNA synthesis. Inhibition of 125I-labeled epidermal growth factor binding and stimulation of 86Rb+ uptake by vasopressin are also selectively decreased in the refractory cells. The vasopressin receptors that mediate mitogenesis in Swiss 3T3 cells are of the pressor type, not coupled to adenylate cyclase. These cells bind [3H]vasopressin in a specific and saturable (Kd = 1 X 10(-8) M) manner. The receptors are down-regulated after prolonged vasopressin treatment; however, this cannot provide a complete explanation of desensitization because cells that are completely refractory to vasopressin retain 60% of their [3H]vasopressin binding sites. Vasopressin refractoriness must therefore occur partly at a post-receptor locus.