Molecular and pharmacological characterization of the murine tachykinin NK3 receptor

Starting with a partial sequence from Genbank, polymerase chain reaction (P CR) was utilized to isolate the full-length cDNA for NK3 receptor from mous e brain. The murine NK3 receptor has a predicted sequence of 452 amino acid s, sharing 96% and 86% identity to the rat and human NK3 receptors, respect ively. Binding affinities and functional potencies of tachykinin receptor a gonists were similar in HEK (human embryonic kidney) 293 cells expressing m urine NK3 receptor and human NK3 receptor, although substance P and neuroki nin A were more potent stimulators of Ca2+ mobilization in murine NK3 recep tor cells. NK3 receptor-selective antagonists from two structural classes, had 10- to 100-fold lower binding affinities for murine NK3 receptor compar ed to human NK3 receptor, and about 5- to 10-fold reduced potency in the mu rine NK3 receptor functional assay. The results demonstrate species differe nces in the potencies of tachykinin receptor antagonists in murine and huma n NK3 receptors, and the lower potencies in the former should be taken into consideration when using murine disease models. (C) 2001 Elsevier Science B.V. All rights reserved.