The F1-ATPase beta-subunit is the putative enterostatin receptor.

It has been suggested that the F1-ATPase beta-subunit is the enterostatin receptor. We investigated the binding activity of the purified protein with a labeled antagonist, beta-casomorphin1-7, in the absence and presence of cold enterostatin. 125I-beta-casomorphin1-7 weakly binds to the rat F1-ATPase beta-subunit. Binding was promoted by low concentrations of cold enterostatin but displaced by higher concentrations. To study the relationship between binding activity and feeding behavior, we examined the ability of a number of enterostatin analogs to affect beta-casomorphin1-7 binding to the F1-ATPase beta-subunit. Peptides that suppressed food intake promoted beta-casomorphin1-7 binding whereas peptides that stimulated food intake or did not affect the food intake displaced beta-casomorphin1-7 binding. Surface plasmon resonance measurements show that the beta-subunit of F1-ATPase binds immobilized enterostatin with a dissociation constant of 150 nM, where no binding could be detected for the assembled F1-ATPase complex. Western blot analysis showed the F1-ATPase beta-subunit was present on plasma and mitochondrial membranes of rat liver and amygdala. The data provides evidence that the F1-ATPase beta-subunit is the enterostatin receptor and suggests that enterostatin and beta-casomorphin1-7 bind to distinct sites on the protein.