Vasopressin induces selective desei response in Swiss 3T3 cells (DNA synthesis/growth control/vasopressin receptor/down regulatio

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 fac- tor. This desensitization is selective for vasopressin, requires pro- longed incubation (half-maximal desensitization after 12 hr of treatment) for its induction, and is reversed after a 48-hr incu- bation in the absence of vasopressin. It is elicited by concentra- tions of vasopressin, and several analogues, similar to those re- quired 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 pro- longed vasopressin treatment; however, this cannot provide a complete explanation of desensitization because cells that are completely refractory to vasopressin retain 60% of their (3H)va- sopressin binding sites. Vasopressin refractoriness must therefore occur partly at a post-receptor locus.