Article ; Online: Drug action of benzocaine on the sarcoplasmic reticulum Ca-ATPase from fast-twitch skeletal muscle.
Naunyn-Schmiedeberg's archives of pharmacology
2015 Volume 388, Issue 11, Page(s) 1163–1170
Abstract: The effect of the local anesthetic benzocaine on sarcoplasmic reticulum membranes isolated from fast-twitch muscles was tested. The effects on Ca-ATPase activity, calcium binding and uptake, phosphoenzyme accumulation and decomposition were assessed ... ...
Abstract | The effect of the local anesthetic benzocaine on sarcoplasmic reticulum membranes isolated from fast-twitch muscles was tested. The effects on Ca-ATPase activity, calcium binding and uptake, phosphoenzyme accumulation and decomposition were assessed using radioisotopic methods. The calcium binding to the Ca-ATPase was noncompetitively inhibited, and the enzymatic activity decreased in a concentration-dependent manner (IC50 47.1 mM). The inhibition of the activity depended on the presence of the calcium ionophore calcimycin and the membrane protein concentration. The pre-exposure of the membranes to benzocaine enhanced the enzymatic activity in the absence of calcimycin, supporting the benzocaine permeabilizing effect, which was prevented by calcium. Benzocaine also interfered with the calcium transport capability by decreasing the maximal uptake (IC50 40.3 mM) without modification of the calcium affinity for the ATPase. It inhibited the phosphorylation of the enzyme, and at high benzocaine concentration, the dephosphorylation step became rate-limiting as suggested by the biphasic profile of phosphoenzyme accumulation at different benzocaine concentrations. The data reported in this paper revealed a complex pattern of inhibition involving two sites for interaction with low and high benzocaine concentrations. It is concluded that benzocaine not only exerts an indirect action on the membrane permeability to calcium but also affects key steps of the Ca-ATPase enzymatic cycle. |
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MeSH term(s) | Anesthetics, Local/pharmacology ; Animals ; Benzocaine/pharmacology ; Calcium/metabolism ; In Vitro Techniques ; Male ; Muscle Fibers, Fast-Twitch/drug effects ; Muscle Fibers, Fast-Twitch/metabolism ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism ; Rabbits ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism |
Chemical Substances | Anesthetics, Local ; Sarcoplasmic Reticulum Calcium-Transporting ATPases (EC 3.6.3.8) ; Calcium (SY7Q814VUP) ; Benzocaine (U3RSY48JW5) |
Language | English |
Publishing date | 2015-11 |
Publishing country | Germany |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 121471-8 |
ISSN | 1432-1912 ; 0028-1298 |
ISSN (online) | 1432-1912 |
ISSN | 0028-1298 |
DOI | 10.1007/s00210-015-1149-7 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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