Development of an anti-idiotypic antibody that blocks substance P primary antibodies and substance P membrane binding.

Polyclonal antibodies against substance P were raised in rabbits and partially purified. This apparently homogeneous immunoglobulin fraction was used to immunize other rabbits. The anti-idiotypic antibodies derived from these rabbits were substantially more effective in competing with substance P than in competing with beta-endorphin for binding to their respective primary antibodies. The anti-idiotypic antibody was also 50 times more potent in competing with substance P binding than in competing with substance K binding to rat duodenal membranes, a tissue containing receptors for substance P and substance K. The anti-idiotypic antibodies exhibited significant enhancement of substance P induced spasmogenic response on the rat uterus and guinea pig ileum (GPI). The results indicate that it is possible to develop anti-idiotypic antibodies that recognize substance P receptors. These antibodies will be of value in studies of the physiological roles of the neuropeptide, substance P.