Opioid receptor-like (ORL1) receptor utilizes both G(oA) and G(oB) for signal transduction.

The ORL1 receptors stably expressed in HEK 293 cells can utilize PTX-resistant mutants of Galpha(oA/B) to inhibit adenylyl cyclase (AC) and stimulate extracellular signal-regulated protein kinases (ERKs). However, development of AC superactivation and loss of ERK1/2 responsiveness induced by chronic activation of the ORL1 receptors remained PTX-sensitive.