Multiple intracellular signaling pathways of the neuropeptide substance P receptor.
The rat substance P (SP) receptor cDNA has been transfected into cultured rat KNRK cells, and a stable cell line expressing functional SP receptors established. Upon stimulation with SP, these cells responded by simultaneously activating two signaling pathways: the mobilization of intracellular Ca2+ and the raising of cyclic adenosine triphosphate (cAMP) levels. Both Ca2+ and cAMP responses were elicited in a similar dose-dependent manner with half maximal concentrations of approximately 5 x 10(-10) M. Following ionomycin treatment SP-dependent Ca2+ responses were abolished, whereas cAMP responses were preserved. Forskolin eliminated the SP-dependent cAMP elevation, however, the SP-induced Ca2+ mobilization remained unchanged. Furthermore, treatment with phorbol esters had no significant effect on either of the two SP-induced responses. Thus it appears that the SP receptor is capable of independently activating Ca2+ mobilization and cAMP pathways. These results may provide new insights for further understanding the diverse activities of SP in various systems in vitro and in vivo.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis; D016257:Fura-2; D007457:Iodine Radioisotopes; D011493:Protein Kinase C / Q000032:analysis / Q000378:metabolism; D051381:Rats; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013373:Substance P / Q000378:metabolism; D014162:Transfection
D007457:Iodine Radioisotopes; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D005576:Colforsin; D013373:Substance P; D011493:Protein Kinase C; D006152:Cyclic GMP; D002118:Calcium; D016257:Fura-2