Ketamine stimulates secretion of beta-endorphin from a mouse pituitary cell line.
OBJECTIVE
beta-endorphin is an endogenous opioid that mediates pain-induced analgesia. Propofol inhibits in vitro secretion of beta-endorphin from a mouse pituitary cell line (AtT-20). We hypothesized that ketamine would also alter secretion of beta-endorphin.


METHODS
AtT-20 cells were exposed to the intravenous anesthetic ketamine (10 to 40 micromol/L). Secretion of beta-endorphin was determined by enzyme-linked immunosorbent assay. Long-term effects were determined by exposing the cells to ketamine, allowing the cells to recover overnight, then stimulating the secretion of beta-endorphin. AtT-20 cells were stimulated with secretagogues to induce secretion of beta-endorphin. The effect of ketamine on stimulated secretion was determined. Cultures of AtT-20 cells were grown for 5 days in the presence of ketamine. Cell numbers were determined on each day.


RESULTS
Ketamine increased secretion of beta-endorphin to levels that were up to 3 times greater than baseline secretion. Stimulation of beta-endorphin secretion by ketamine persisted into the subsequent day. Ketamine caused increased secretion from cells stimulated with secretagogues. Ketamine was not toxic to these cells; AtT-20 cells grew normally for 5 days in the presence of up to 40 micromol/L ketamine.


CONCLUSIONS
Clinically relevant concentrations of ketamine stimulated both immediate and delayed secretion of beta-endorphin. This suggests that the prolonged analgesia observed in some clinical situations with ketamine could be in part caused by increased release of an endogenous opioid.
YaDeau
Jacques T
JT
Department of Anesthesiology, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York, USA. yadeauj@hss.edu
Morelli
Christine M
CM
Billingsley
John-Kenneth
JK
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D007649:Ketamine / Q000494:pharmacology*; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical; D001615:beta-Endorphin / Q000378:metabolism*
D000778:Anesthetics, Dissociative; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015240:Phorbol 12,13-Dibutyrate; D001615:beta-Endorphin; D007649:Ketamine