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Membranes isolated from a murine fibroblast B82 cell line (SKLKB82#3) transfected with the bovine stomach cDNA pSKR56S exhibited binding of [His('25I) Considerable physiological and biochemical evidence exists for distinct NK1-, NK2-, and NK3-tachykinin peptide receptors. The preferred endogenous ligand appears to be substance P (SP) for NK1 receptors, neurokinin A (NKA) for NK2 receptors, and neurokinin B for NK3 receptors (1-4). Nakanishi and coworkers have cloned and expressed in Xenopus oocytes three tachykinin receptors-the rat brain NK1 receptor, the rat brain NK3 receptor, and the bovine stomach NK2 receptor (5-8). A functional cDNA encoding the rat SP receptor was also recently characterized by Hershey and Krause (9). The NK2 receptor has a calculated molecular mass of 43,066 Da, and all three receptors appear to be putative guanine nucleotide-binding protein (G protein)-linked receptors, each with seven hydrophobic, membranespanning domains, an extracellular amino terminus, and a cytoplasmic carboxyl terminus.The primary structures of numerous neurotransmitter receptors have been determined, but few of these are neuropeptide receptors (10,11). Recently, the bovine stomach cDNA, pSKR56S, was transfected into the murine fibroblast B82 cell line to produce cells (SKLKB82#3) with a high

Neuropeptide K (NPK) and neuropeptide gamma (NP gamma) are two endogenous N-terminally extended forms of neurokinin A (NKA). Here, we compared their effects with those of NKA on 125I-NKA binding, phosphatidylinositol (PI) turnover and smooth muscle contraction in the hamster urinary bladder. NPK, NP gamma and NKA were equipotent in competing 125I-NKA from NK2 receptors in crude hamster bladder membranes. All three peptides stimulated PI turnover by approximately 750% with similar potency. In a third series of experiments, these peptides had similar efficacy in inducing a dose-dependent contraction of bladder smooth muscle. The NK2 receptor selective antagonist L-659,877 (cyclo[Leu-Met-Gln-Trp-Phe-Gly]) inhibited the stimulation of PI turnover and bladder contractions induced by all three tachykinins. The present results show that NKA, NPK and NP gamma display a similar biological profile. The N-terminal extensions of NPK and NP gamma appear not to influence binding of these peptides to NK2 receptors, NK2 receptor mediated stimulation of PI turnover, or smooth muscle contraction in hamster urinary bladder.

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