[Volatile anesthetics and n-alcohols inhibit the uptake of noradrenaline in pheochromocytoma cells].
Studies with perfused animal organs did not show a significant inhibition of the norepinephrine uptake by volatile anesthetics However, the uptake of norepinephrine into isolated chromaffin granules proved to be halothane-sensitive , and there is indirect evidence for an inhibition of norepinephrine uptake by halothane in the dog saphenous vein. So far no literature is available on norepinephrine uptake into cultured cells in the presence of volatile anesthetics. The rat pheochromocytoma cell line PC 12, which shares many properties with adrenal medulla cells and also with sympathetic neurons, has been used as a model to study norepinephrine uptake and release. One of its properties in common with sympathetic neurons is the high-affinity uptake system for norepinephrine. Therefore, we have used PC 12 cells as a pharmacologically well-established model system to study the effect of general anesthetics on the uptake of norepinephrine.


METHODS
The experiments were performed with monolayers of PC 12 cells on 3 cm petri dishes. The cells were allowed to take up tritiated norepinephrine (0.25 microCI/ml) for 20 min at 36 degrees C in the presence and absence of general anesthetics.


CONCLUSIONS
The volatile anesthetics halothane, enflurane, isoflurane, and methoxyflurane in clinical relevant concentrations inhibited the high-affinity uptake of tritiated norepinephrine into the PC 12 cells (Fig. 1). We could further show an inhibition of norepinephrine uptake by n-alkanols at concentrations that cause anesthesia in tadpoles. Fig. 2 illustrates that a good correlation (r = 0.997 for the n-alkanols, r = 0.934 for the volatile anesthetics) exists between anesthetic potency and the IC50 for norepinephrine uptake inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Tas
P W
PW
Institut für Virologie und Immunbiologie, Universität Würzburg.
Kress
H G
HG
Koschel
K
K
D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000438:Alcohols / Q000494:pharmacology*; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D004737:Enflurane / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D007700:Kinetics; D008733:Methoxyflurane / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010673:Pheochromocytoma / Q000378:metabolism*
D000438:Alcohols; D000777:Anesthetics; D008733:Methoxyflurane; D004737:Enflurane; D007530:Isoflurane; D006221:Halothane; D009638:Norepinephrine
Volatile Anaesthetika und n-Alkanole hemmen die Aufnahme von Noradrenalin in Phäochromozytom-Zellen.