Drug action of benzocaine on the sarcoplasmic reticulum Ca-ATPase from fast-twitch skeletal muscle

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.

Solubility of Ethyl p-Aminobenzoate in Six Alcohols within (283.15 to 327.15) K

“…94-09-7) is a white crystal without smell and widely used in chemical and pharmaceutical industry. As an important local anesthetic, it is extremely effective in relieving pain caused by traumatic injury, skin ulcers, and burn. − EPAB also acts as an additive in cosmetics to absorb ultraviolet light, and it plays an increasingly vital role in commercial fish farms . In addition, EPAB can be applied in the synthesis of biological activity compounds, such as a series of new 5-substituted aryl/aralkyl-1,3,4-oxadiazol-2-yl 4-(morpholin-4-ylsulfonyl) benzyl sulfides, cN-(4-ethoxycarbonylphenyl)-5,6,8,9-tetrahydro-7-phenyl­dibenzo­[c,h]­acridinium perchlorate, and 2-((5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)­thiomethyl)-1-benzyl benzimidazole .…”