[Modulatory effects of barbiturates and their binary combinations on human alpha-1 glycine receptors expressed in Xenopus Oocytes]

ABSTRACT

To test whether there is a common site of action for intravenous anaesthetics at the glycine receptor, the effects of binary combinations of thiopentone, pentobarbitone, and methohexitone have been tested on human alpha 1 glycine receptors expressed in Xenopus laevis oocytes using two-electrode voltage-clamp techniques. During this interventional study, recombinant human alpha-1 receptor gene was prepared and the mRNA was injected into cytoplasmic site of Xenopus oocytes. Two-electrod voltage clamp technique used for pharmacological studies of currents of chloride channels [receptors] from the membrane of oocytes. Then, the effect of three barbiturates on currents induced by agonist on the receptors was measured. Thiopentone [5-40microM], and pentobarbitone [25-400microM], [but not methohexitone] potentiated the glycine-induced [50microM] current in a dose-dependent manner, with the maximum potentiation observed to be 220%, and 400%, respectively. In binary combination with thiopentone, or pentobarbitone, methohexitone reduced potentiation compared to that by the individual anesthetics to 180%, and 280%, respectively. Combination of thiopentone and pentobarbitone [50microM] increased potentiation, compared to that by thiopentone alone. Our results indicate that thiopentone and pentobarbitone both act as positive allosteric modulators at the alpha-1 glycine receptor. In contrast, methohexitone has no action alone but acts as a competitive antagonist to thiopentone and pentobarbitone. We suggest that these three intravenous barbiturate anaesthetics share a common site of action at the glycine receptor