Canadian Journal of Anaesthesia

, Volume 47, Issue 5, pp 467–470 | Cite as

Effects of intravenous and local anesthetic agents on ω-conotoxin MVIIA binding to rat cerebrocortex

Brief Reports


Purpose: The cellular target site(s) for anesthetic action remain controversial. In this study we have examined any interaction of iv anesthetics (thiopental, pentobarbital, ketamine, etomidate, propofol, alphaxalone), local anesthetics (lidocaine, prilocaine, procaine and tetracaine), and the non anesthetic barbiturate, barbituric acid with the ω-conotoxin MVIIA binding site on N-type voltage sensitive Ca2+ channels in rat cerebrocortical membranes.

Methods: [125I] ω-conotoxin MVIIA binding assays were performed in 0.5 ml volumes of Tris.HCL buffer containing BSA 0.1% for 30 min at 20°C using fresh cerebrocortical membranes (5 µg of protein). Non-specific binding was defined in the presence of excess (10−8 M) ω-conotoxin MVIIA. The interaction of iv (alphaxolone, etomidate, propofol, pentobarbitone, ketamine and thiopentone), local (lidocaine, prilocaine, procaine and tetracaine) anesthetics and barbituric acid was determined by displacement of [125I] ω -conotoxin MVIIA (∼ 1 pM).

Results: The binding of [125I] ω -conotoxin was concentration-dependent and saturable with Bmax and Kd of 223±15 fmol/mg protein and 2.13±0.14 pM, respectively. Unlabelled ω -conotoxin MVIIA displaced [125I] ω -conotoxin MVIIA yielding a pKd of 11.04±0.04 (9.2 pM). All iv and local anesthetics at dinically relevant concentrations did not show any interaction with the ω-conotoxin MVIIA binding site.

Conclusion: The present study suggests that ω-conotoxin MVIIA binding site on N-type voltage sensitive Ca2+ channels may not be a target for iv and local anesthetic agents.


Dexmedetomidine Etomidate Procaine Local Anesthetic Agent Barbituric Acid 
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Objectif: L’existence de sites cellulaires cibles pour l’action des anesthésiques demeure controversée. La présente étude a examiné toutes les interaction des anesthésiques iv (thiopental, pentobarbital, kétamine, étomidate, propofol, alphaxalone), et locaux (lidocaïne, prilocaïne, procaïne et tétracaïne), des barbituriques non anesthésiques et de l’acide barbiturique avec le site de fixation de la T-conotoxine MVIIA sur les canaux Ca2+vol-tage-dépendants de type N, localisés sur des membranes cérébrocorticales de rats.

Méthode: Des essais de fixation avec la [125I] T-conotoxine MVIIA ont été réalisés dans 0,5 ml de tampon Tris. HCL contenant de l’albumine de sérum de boeuf (ASB) à 0,1 % pendant 30 min à 20 °C en utilisant des membranes cérébrocorticales fraîches (5 µg de protéine). La fixation était jugée non spécifique en présence d’un excès (10−8 M) de T-conotoxine MVIIA. L’interaction des anesthésiques iv (alphaxolone, étomidate, propofol, pentobarbital, kétamine et thiopental), locaux (lidocaïne, prilocaïne, procaïne et tétracaïne) et de l’acide barbiturique a été déterminée par le déplacement de la [125I]T-conotoxine MVIIA (∼ 1 pM).

Résultats: La fixation de la [125I]T -conotoxine était dépendante de la concentration et saturable avec Bmax et Kd de 223±15 fmol/mg de protéine et 2,13±0,14 pM, respectivement. La T-conotoxine MVIIA non marquée a déplacé la [125I] T -conotoxine MVIIA fournissant un pKd de 11,04±0,04 (9,2 pM). Tous les anesthésiques iv et locaux en concentrations applicables en clinique n’ont pas montré d’interaction avec le site de fixation de la T-conotoxine MVIIA.

Conclusion: L’étude suggère que le site de fixation de la T-conotoxine MVIIA sur les canaux Ca2+ voltage-dépendants de type N, ne serait peut-être pas une cible pour les anesthésiques iv et locaux.


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Copyright information

© Canadian Anesthesiologists 2000

Authors and Affiliations

  1. 1.From the University Department of Anaesthesia and Pain ManagementLeicester Royal InfirmaryLeicesterUK
  2. 2.Department of AnesthesiologyUniversity of Hirosaki School of MedicineHirosakiJapan

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