Signaling pathways via NK1 receptors and their desensitization in an AR42J cell line.
Substance P (SP) has been shown to induce phosphatidylinositol (PI) hydrolysis and Ca2+ mobilization in AR42J cells. In this study, we confirmed the expression of NK1 but not NK2 or NK3 receptors in this cell line, and further investigated signaling pathways via NK1 receptors and their desensitization. The activation of NK1 receptors by SP affected neither basal cyclic AMP level nor cyclic AMP accumulation induced by secretin and forskolin, although it stimulated PI hydrolysis. Furthermore, SP induced Ca2+ mobilization even in the absence of extracellular Ca2+, though maximal response was reduced. U73122, a phospholipase C (PLC) inhibitor, nearly abolished Ca2+ response to SP. In addition, SP-induced Ca2+ signaling and PI hydrolysis rapidly desensitized following short exposure to SP, which did not affect the Ca2+ amount in intracellular Ca2+ stores or Ca2+ responses to carbachol and gastrin releasing peptide-10. These findings suggested that NK1 receptors do not couple to adenylate cyclase, although they induce PI response, and that NK1 receptors induce both intracellular Ca2+ release and Ca2+ influx through PLC activation. Ca2+ signaling and PI hydrolysis through NK1 receptors desensitized rapidly after the stimulation, maybe dependent on the modification of NK1 receptors.
Fukuhara
S
S
Institute of Applied Biochemistry, University of Tsukuba, Ibaraki, Japan.
Shimizu
M
M
Matsushima
H
H
Mukai
H
H
Munekata
E
E
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D018267:Carcinoma, Acinar Cell / Q000737:chemistry / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism; D003888:Desensitization, Immunologic / Q000379:methods*; D006868:Hydrolysis; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000473:pathology; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D010716:Phosphatidylinositols; D018040:Receptors, Neurokinin-1; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; D000242:Cyclic AMP