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  • Title: Multiple intracellular signaling pathways of the neuropeptide substance P receptor.
    Author: Mitsuhashi M, Ohashi Y, Shichijo S, Christian C, Sudduth-Klinger J, Harrowe G, Payan DG.
    Journal: J Neurosci Res; 1992 Jul; 32(3):437-43. PubMed ID: 1279191.
    Abstract:
    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.
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