While Gβγ in pancreatic acini cells was shown to also directly activate IP3R independent of IP3 production, causing ER Ca2+ release (Zeng et al., 2003), the inability of gallein to inhibit D,L-methadone-induced ER Ca2+ release, and the ability of PTx to completely inhibit D,L-methadone-induced ER Ca2+ release indicate that D,L-methadone-induced ER Ca2+ release in leukemia cells does not involve direct activation of IP3R by Gβγ. This evidence concerns the gene CFB and leukemia.