دورية أكاديمية
أعرض في EDS

A common local anesthetic receptor for benzocaine and etidocaine in voltage-gated mu1 Na+ channels.

التفاصيل البيبلوغرافية
العنوان: A common local anesthetic receptor for benzocaine and etidocaine in voltage-gated mu1 Na+ channels.
المؤلفون: Wang GK; Department of Anesthesia, Brigham and Women's Hospital, 75 Francis St. Boston, MA 02115, USA., Quan C, Wang S
المصدر: Pflugers Archiv : European journal of physiology [Pflugers Arch] 1998 Jan; Vol. 435 (2), pp. 293-302.
نوع المنشور: Journal Article; Research Support, U.S. Gov't, P.H.S.
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: Germany NLM ID: 0154720 Publication Model: Print Cited Medium: Print ISSN: 0031-6768 (Print) Linking ISSN: 00316768 NLM ISO Abbreviation: Pflugers Arch Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Berlin, New York, Springer.
مواضيع طبية MeSH: Anesthetics, Local/*pharmacology , Benzocaine/*pharmacology , Etidocaine/*pharmacology , Receptors, Drug/*analysis , Sodium Channels/*chemistry , Sodium Channels/*drug effects, Amino Acid Sequence ; Anesthetics, Local/metabolism ; Benzocaine/metabolism ; Cell Line ; Electric Conductivity ; Embryo, Mammalian ; Etidocaine/metabolism ; Humans ; Kidney ; Lidocaine/analogs & derivatives ; Lidocaine/pharmacology ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Receptors, Drug/chemistry ; Receptors, Drug/metabolism ; Sodium Channels/genetics
مستخلص: According to Hille's modulated receptor hypothesis, benzocaine shares a common receptor with all other local anesthetics (LAs) in the voltage-gated Na+ channel. We tested this single receptor hypothesis using mutant muscle Na+ channels of mu1-I1575A, F1579A, and N1584A transiently expressed in Hek-293t cells. Both benzocaine and etidocaine are more effective at blocking mu1-N1584A current than the wild-type current, while they are less potent at blocking mu1-F1579A current. Such concurrent changes of both benzocaine and etidocaine potency towards F1579A and N1584A mutants suggest that they share a common LA receptor. Consistent with results found in studies of native Na+ channels, permanently charged QX-314 at 1 mM is not effective at blocking wild-type, F1579A, and N1584A current via external application. In contrast, QX-314 is relatively potent at blocking I1575A current when applied externally. This increased potency of external QX-314 against the mu1-I1575A mutant has been reported previously in a study of the brain counterpart. Mutant I1575A also appears to be highly sensitive to the external divalent cation Cd2+, probably because of the presence of cysteine residues near the mu1-I1575 position in the IV-S6 segment. To our surprise, neutral benzocaine becomes more effective at blocking mu1-I1575A current than the wild-type current, whereas the opposite is found for etidocaine. We hypothesize that an increase in accessibility of external QX-314 to the mu1-I1575A mutant is accompanied by a reduction of binding towards the charged amine component.
معلومات مُعتمدة: GM-35401 United States GM NIGMS NIH HHS; GM-48090 United States GM NIGMS NIH HHS
المشرفين على المادة: 0 (Anesthetics, Local)
0 (Receptors, Drug)
0 (Sodium Channels)
21306-56-9 (QX-314)
98PI200987 (Lidocaine)
I6CQM0F31V (Etidocaine)
U3RSY48JW5 (Benzocaine)
تواريخ الأحداث: Date Created: 19980207 Date Completed: 19980205 Latest Revision: 20190726
رمز التحديث: 20221213
DOI: 10.1007/s004240050515
PMID: 9382945
قاعدة البيانات: MEDLINE
الوصف
تدمد:0031-6768
DOI:10.1007/s004240050515