A truncated delta opioid receptor, spontaneously produced in human but not rat neuroblastoma cells, interferes with signaling of the full-length receptor.

In addition to the established human delta opioid receptor SH-SY5Y neuroblastoma cells produce an atypical, shorter, form of this receptor which is predicted to lack the third intracellular domain. Hence it will be referred to as hdelta(deltaICD3). Notably, in unaltered human brain tissue only the established ('wild type') delta receptor was detected. After transfection of the human wild type delta receptor (hdelta(wt)) into NG 108-15 rodent neuroblastoma-derived cells, HEK 293 human embryonic kidney cells and NIH 3T3 mouse fibroblasts, all these cell types produced hdelta(deltaICD3). Only the human but not the rat delta opioid receptor was processed, arguing for a high sequence selectivity of the cleavage process. Upon agonist stimulation hdelta(deltaICD3) was not able to activate potassium channels (K(ir)3.1/K(ir)3.4) expressed in Xenopus laevis oocytes. However, hdelta(deltaICD3) dose-dependently inhibited the signaling of hdelta(wt) if co-expressed with the latter. Thus, hdelta(deltaICD3) can be produced by many cell types and, once produced, markedly interferes with normal delta receptor signaling.