NOCICEPTIN stimulation of the ORL1 receptor expressed in Chinese hamster ovary (CHO) cells results in the activation of the extracellular signal regulated kinases ERK1 and ERK2. ERK1/ERK2 activation is inhibited by pertussis toxin, the MEK inhibitor PD 98059 and by transient expression o α-transducin, indicating that ORL1 up-regulation of these kinases occurs as a consequence of the release of the G-protei n βγ complex following the activation of pertussis-toxin sensitive Gαi-family G-proteins. Using specific reporter genes we demonstrate that the transcription factors Elk-1 and Sap1a are activated in a pertussis toxin-sensitive manner as a consequence of ORL1 upregulation of ERK1/ERK2 to induce changes in gene expression. The activation of these transcription factors is also inhibited following treatment with PD 98059 and following coexpression of α-transducin.