MULTIPLE INTRACELLULAR SIGNALING PATHWAYS OF THE NEUROPEPTIDE SUBSTANCE-P RECEPTOR

被引:70
作者
MITSUHASHI, M
OHASHI, Y
SHICHIJO, S
CHRISTIAN, C
SUDDUTHKLINGER, J
HARROWE, G
PAYAN, DG
机构
[1] UNIV CALIF SAN FRANCISCO, HOWARD HUGHES MED INST LABS, SAN FRANCISCO, CA 94143 USA
[2] UNIV CALIF SAN FRANCISCO, DEPT MED, SAN FRANCISCO, CA 94143 USA
[3] UNIV CALIF SAN FRANCISCO, DEPT MICROBIOL & IMMUNOL, SAN FRANCISCO, CA 94143 USA
关键词
CAMP; CA2+; TRANSFECTION; PROTEIN KINASE-C;
D O I
10.1002/jnr.490320315
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:437 / 443
页数:7
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