Inhibition of regulated neuropeptide secretion from mouse pituitary cells by propofol.
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 microM. The propofol IC50 values for secretion stimulated by other secretagogs were 47 microM (barium), 42 microM (Bay K 8644, a calcium channel agonist), and 28 microM (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 microM propofol. The finding suggests that propofol inhibited a site in neuropeptide exocytosis common to the three studied pathways of secretion.
YaDeau
J T
JT
Department of Anesthesiology, Cornell University Medical College, New York, New York 10021, USA. jayadea@med.cornell.edu
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002460:Cell Line; D002712:Chlorides / Q000494:pharmacology; D007118:Immunoassay; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010902:Pituitary Gland / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology*; D001615:beta-Endorphin / Q000378:metabolism*
D018686:Anesthetics, Intravenous; D017609:Barium Compounds; D002120:Calcium Channel Agonists; D002712:Chlorides; C024986:barium chloride; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015240:Phorbol 12,13-Dibutyrate; D001615:beta-Endorphin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015742:Propofol