The mechanism of inhibitory actions of propofol on rat supraoptic neurons.
BACKGROUND
In the perioperative period, plasma osmotic pressure, systemic blood pressure, and blood volume often change dramatically. Arginine vasopressin is a key factor in the regulation of these parameters. This study was performed to evaluate the direct and the mechanism of the actions of propofol on arginine vasopressin release from magnocellular neurosecretory neurons in the rat supraoptic nucleus.


METHODS
Somatodendritic arginine vasopressin release from supraoptic nucleus slice preparations was measured by radioimmunoassay. Ionic currents were measured using the whole-cell mode of the patch-clamp technique in supraoptic nucleus slice preparations or in single dissociated supraoptic nucleus neurons of the rat.


RESULTS
Propofol at concentrations greater than 10(-5) M inhibited the arginine vasopressin release stimulated by potassium chloride (50 mM). This inhibition by propofol was not reversed by picrotoxin, a gamma-aminobutyric acid(A)(GABA(A)) receptor antagonist, whereas arginine vasopressin release induced by glutamate (10(-3) M) was also inhibited by propofol at a clinically relevant concentration (10(-6) M). The latter effect was reversed by picrotoxin. Propofol evoked Cl- currents at concentrations ranging 10(-6) to 10(-4) M. Propofol (10(-6) M) enhanced the GABA (10(-6) M)-induced current synergistically. Moreover, propofol (10(-6) M) prolonged the time constant of spontaneous GABA-mediated inhibitory postsynaptic currents. Furthermore, propofol (10(-5) M and 10(-4) M) reversibly inhibited voltage-gated Ca2+ currents, whereas it did not affect currents induced by glutamate (10(-3) M).


CONCLUSIONS
Propofol inhibits somatodendritic arginine vasopressin release from the supraoptic nucleus, and the enhancement of GABAergic inhibitory synaptic inputs and the inhibition of voltage-gated Ca2+ entry are involved in the inhibition of arginine vasopressin release.
Inoue
Y
Y
Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan. y-inouwe@med.uoeh-u.ac.jp
Shibuya
I
I
Kabashima
N
N
Noguchi
J
J
Harayama
N
N
Ueta
Y
Y
Sata
T
T
Shigematsu
A
A
Yamashita
H
H
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013495:Supraoptic Nucleus / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D007473:Ion Channels; D001127:Arginine Vasopressin; D005680:gamma-Aminobutyric Acid; D002118:Calcium; D015742:Propofol