An analog of the Neurokinin B peptide, [MePhe7]-NKB, is a selective agonist of the NK3 receptor. Conjugation of [MePhe7]-NKB to saporin (NK3-SAP) allows for the specific elimination of a subpopulation of neurons expressing kisspeptin, neurokinin B, and dynorphin (KNDy neurons) through their co-expression of the NK3 receptor. Although NK3 receptor expressing neurons reside in several locations, KNDy neurons reside only within the hypothalamic arcuate nucleus of many mammalian species and are critical for reproductive function. NK3-SAP can also be used to target and selectively destroy NK3r-expressing cells in other regions of the brain.
NK3-SAP (molecular weight 31.5 kDa) is a chemical conjugate of neurokinin B and the ribosome-inactivating protein, saporin, and has been used to examine the role of KNDy neurons in the estrogen regulation of LH secretion and body weight in female rats (see cover article, pages 1 and 6).