NOCICEPTION ACTIVATES ELK-1 AND SAP1A FOLLOWING EXPRESSION OF THE ORL1 RECEPTOR IN CHINESE-HAMSTER OVARY CELLS

NOCICEPTIN stimulation of the ORL1 receptor expressed in Chinese hamst er ovary (CHO) cells results in the activation of the extracellular si gnal regulated kinases ERK1 and ERK2. ERK1/ERK2 activation is inhibite d by pertussis toxin, the MEK inhibitor PD 98059 and by transient expr ession of alpha-transducin, indicating that ORL1 up-regulation of thes e kinases occurs as a consequence of the release of the G-protein beta gamma complex following the activation of pertussis-toxin sensitive G alpha(i)-family G-proteins. Using specific reporter genes we demonstr ate that the transcription factors Elk-l and Sapla 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 alpha-transducin. (C) 1998 Lip pincott Williams & Wilkins.