title: The effects of local anaesthetics on the electrical and mechanical activity of the guinea-pig ureter.
abstract: The effects of local anaesthetic tertiary amines (procaine, lignocaine and tetracaine) as well as neutral (benzocaine) and permanently charged (QX-314) local anaesthetics were studied on the evoked electrical and mechanical activity of the ureter smooth muscle. 'Low' concentrations of procaine and lignocaine (0.1-1mM) at pH 7.4 increased the duration of the slow plateau component of the evoked action potentials. The amplitude of the phasic contraction was consequently increased within the first 5 min of exposure. Tetracaine 0.1 mM caused a transient increase in the duration of the plateau and amplitude of the phasic contraction within the first 1-2 min only. The stimulant action of the local anaesthetics was greatly reduced in the presence of tetraethylammonium (TEA). All the tertiary local anaesthetics caused depolarization of the membrane accompanied by an increase in the size of the electronic potentials. Lignocaine normally initiated the discharge of spontaneous action potentials. High concentrations of lignocaine (5 mM) and tetracaine (0.5 mM) caused complete inhibition of the evoked action potentials and phasic contractions. Procaine 5 mM predominantly inhibited the contractile responses. The permanently charged local anaesthetic QX-314 (1 mM) caused an increase in the duration and amplitude of the plateau, increasing the number of spikes and the amplitude and duration of the phasic contraction. It also depolarized the ureter smooth muscle cells increasing the size of electronic potentials. The neutral local anaesthetic benzocaine at 1 mM caused a reversible selective blockade of the plateau component of the evoked action potential and a gradual reduction in the amplitude of the phasic contraction. No change in either the membrane potential or the membrane conductance was observed. 7 High pH. (pH 9) significantly increased while low pH0 (pH 6) decreased the inhibitory action of procaine and lignocaine but did not alter the effects of benzocaine and QX-314. 8 Benzocaine caused a relaxation of the high-K-induced contraction, preferentially blocking the tonic component, whereas QX-314 had no effect on the KC1-contracture of the ureter muscle. 9 Two sites of action in the ureter smooth muscle cell membrane for local anaesthetics are suggested. One site interacts with local anaesthetics in a charged form, while the other one interacts with those in a lipid-soluble neutral form. The charged form of local anaesthetics has a TEA-like action, while the neutral form predominantly causes blockade of 'slow' Na/Ca channels.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009467:Neuromuscular Depolarizing Agents; D011189:Potassium Chloride / Q000494:pharmacology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014513:Ureter / Q000187:drug effects
chemical_list: D000779:Anesthetics, Local; D009467:Neuromuscular Depolarizing Agents; D013757:Tetraethylammonium Compounds; D011189:Potassium Chloride