title: Propofol-induced Inhibition of Catecholamine Release Is Reversed by Maintaining Calcium Influx.
abstract: BACKGROUND
  Propofol (2,6-diisopropylphenol) is one of the most frequently used anesthetic agents. One of the main side effects of propofol is to reduce blood pressure, which is thought to occur by inhibiting the release of catecholamines from sympathetic neurons. Here, the authors hypothesized that propofol-induced hypotension is not simply the result of suppression of the release mechanisms for catecholamines.
  
  
  METHODS
  The authors simultaneously compared the effects of propofol on the release of norepinephrine triggered by high K-induced depolarization, as well as ionomycin, by using neuroendocrine PC12 cells and synaptosomes. Ionomycin, a Ca ionophore, directly induces Ca influx, thus bypassing the effect of ion channel modulation by propofol.
  
  
  RESULTS
  Propofol decreased depolarization (high K)-triggered norepinephrine release, whereas it increased ionomycin-triggered release from both PC12 cells and synaptosomes. The propofol (30 μM)-induced increase in norepinephrine release triggered by ionomycin was dependent on both the presence and the concentration of extracellular Ca (0.3 to 10 mM; n = 6). The enhancement of norepinephrine release by propofol was observed in all tested concentrations of ionomycin (0.1 to 5 μM; n = 6).
  
  
  CONCLUSIONS
  Propofol at clinically relevant concentrations promotes the catecholamine release as long as Ca influx is supported. This unexpected finding will allow for a better understanding in preventing propofol-induced hypotension.
authors.affiliation: From the Department of Anesthesiology (L.H., X.H.) and Department of Thoracic Surgery, Dalian Municipal Friendship Hospital (L.Z.), Dalian Medical University, Dalian, Liaoning, China; Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, Virginia (S.F., G.L.); Department of Urology, the First Affiliated Hospital (Q.L.) and Department of Physiology (A.L.), Dalian Medical University, Dalian, Liaoning, China; Division of Fundamental Neurobiology, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada (L.H., S.G., R.S., S.S.); and Department of Physiology, University of Toronto, Toronto, Ontario, Canada (S.S.).
authors.forename: Liping
authors.initials: L
authors.lastname: Han
authors.forename: Stephen
authors.initials: S
authors.lastname: Fuqua
authors.forename: Quanlin
authors.initials: Q
authors.lastname: Li
authors.forename: Liyu
authors.initials: L
authors.lastname: Zhu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Hao
authors.forename: Aiping
authors.initials: A
authors.lastname: Li
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Gupta
authors.forename: Ravinder
authors.initials: R
authors.lastname: Sandhu
authors.forename: György
authors.initials: G
authors.lastname: Lonart
authors.forename: Shuzo
authors.initials: S
authors.lastname: Sugita
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D015759:Ionomycin / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D016716:PC12 Cells / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D002395:Catecholamines; D006993:Hypnotics and Sedatives; D015759:Ionomycin; D002118:Calcium; D009638:Norepinephrine; D015742:Propofol