Cell shape changes and transmembrane receptor uncoupling induced by tertiary amine local anesthetic

Area of Science:

• Cell Biology
• Pharmacology
• Biochemistry

Background:

• Tertiary amine local anesthetics are known to affect cell morphology and receptor dynamics.
• Concanavalin A (Con A) is a lectin used to study cell surface receptors and their mobility.

Purpose of the Study:

• To investigate the effects of tertiary amine local anesthetics on cell morphology and Con A receptor dynamics.
• To elucidate the mechanisms by which local anesthetics influence cell surface receptor mobility and distribution.

Main Methods:

• Treatment of mouse 3T3 cells and mouse spleen cells with various local anesthetics.
• Assessing Con A-mediated agglutinability and receptor redistribution using fluorescent Con A.
• Utilizing vinblastine, colchicine, and cytochalasin B to mimic anesthetic effects.
• Investigating the role of calcium ions (Ca2+) using Ca2+-specific ionophores (A23187, X537A).

Main Results:

• Low concentrations of local anesthetics enhanced Con A agglutination in 3T3 cells, increasing ligand-induced clustering.
• These drugs inhibited Con A-induced receptor capping on mouse spleen cells.
• The observed effects were mimicked by combinations of microtubule and microfilament inhibitors.
• Ca2+-specific ionophores in the presence of Ca2+ and cytochalasin B replicated the effects of local anesthetics.

Conclusions:

• Tertiary amine local anesthetics likely disrupt microtubule and microfilament assemblies, impacting cell surface receptor mobility.
• The mechanism may involve the displacement of plasma membrane-bound Ca2+, leading to increased intracellular Ca2+ and subsequent disruption of microtubular organization.
• Cellular Ca2+ plays a significant role in the cytoskeletal alterations induced by local anesthetics.