Inhibition of Regulated Neuropeptide Secretion from Mouse Pituitary Cells by Propofol

Abstract

Neuropeptides modulate neuronal responses to stimuli.Secretion of neuropeptides is a potential site for anesthetic action. This paper examines the hypothesis that propofol alters the secretion of beta-endorphin. Cultures of a mouse pituitary cell line (AtT-20) were exposed to propofol in vitro, then induced to secrete beta-endorphin. Secretion was measured by immunoassay. Propofol caused statistically significant inhibition of secretion. Secretion stimulated by phorbol ester was inhibited by propofol with a calculated 50% inhibitory concentration (IC50) value of 48 micro Meter. The propofol IC50 values for secretion stimulated by other secretagogs were 47 micro Meter (barium), 42 micro Meter (Bay K 8644, a calcium channel agonist), and 28 micro Meter (a cyclic adenosine monophosphate [cAMP] analog). AtT-20 cells recovered their ability to secrete beta-endorphin upon removal of the propofol, which demonstrated that they were not damaged permanently by propofol. The effect was relatively specific to neuropeptide secretion, as AtT-20 cells grew normally for 5 days in the presence of 10 or 80 micro Meter propofol. The finding suggests that propofol inhibited a site in neuropeptide exocytosis common to the three studied pathways of secretion. (Anesth Analg 1996;83:611-7)