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Ketamine Stimulates Secretion of β-Endorphin From a Mouse Pituitary Cell Line
  1. Jacques T. YaDeau, M.D., Ph.D.,
  2. Christine M. Morelli, B.S. and
  3. John-Kenneth Billingsley, B.A.
  1. From the Department of Anesthesiology, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York.
  1. Reprint requests: Jacques T. YaDeau, M.D., Ph.D., Division of Anesthesiology, Hospital for Special Surgery, 535 East 70th St, New York, NY, 10021. E-mail: yadeauj{at}


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

Methods AtT-20 cells were exposed to the intravenous anesthetic ketamine (10 to 40 μmol/L). Secretion of β-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 β-endorphin. AtT-20 cells were stimulated with secretagogues to induce secretion of β-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 β-endorphin to levels that were up to 3 times greater than baseline secretion. Stimulation of β-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 μmol/L ketamine.

Conclusions Clinically relevant concentrations of ketamine stimulated both immediate and delayed secretion of β-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. Reg Anesth Pain Med 2003;28:12-16.

  • Anesthetics
  • Intravenous; Ketamine; Neuropeptides
  • β-endorphin

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  • Supported in part by an Anesthesiology Young Investigator Award from the Foundation for Anesthesia Education and Research, and in part by the HSS Anesthesia Research Fund.

    Presented in part at the annual meeting of the International Anesthesia Research Society, Washington D.C. (1996).