The effect of copper on the binding of prostaglandin E1 to NMU-induced rat mammary carcinoma membranes.

Mammary carcinomata were induced by administration of nitrosomethyl urea to female Buffalo rats. Specific binding of PGE1 to the 15,000 xg membranes obtained from these tumors was maximal after approximately 60 minutes of incubation at 15 degrees C. An excess of unlabeled PGE1 dissociated 50% of the [3H]PGE1 from the membrane within 15 minutes. The binding of [3H]PGE1 was inhibited by various prostaglandins in a concentration-dependent manner, the order of potency being PGE1 greater than PGE2 greater than PGA2 greater than PGF2 alpha greater than PGB2. High affinity receptor sites were not definable by Scatchard analysis until 5mM CuCl2 was added. This resulted in the detection of both high and low affinity receptors (Kd = 1.01 nM and 21 microM) having binding capacities of 29 and 357 fmole/mg protein, respectively. Addition of CaCl2 or MgCl2 did not result in a significant increase in the specific binding of PGE1 to the receptors. These studies provide a means by which high affinity prostaglandin E1 receptors can be detected in neoplastic tissue and suggest a mechanism by which copper ions can increase the effect of PGE1 in tissues.