title: Effect of local anesthetics on cellular respiration and thymidine transport in hepatocytes from young and old rats.
abstract: The effect of local anesthetics (procaine, nicotinoyl-procaine, tetracaine, and dibucaine) on thymidine uptake and cellular respiration was investigated in hepatocytes from 3- and 24-month-old rats. All local anesthetics inhibited the "high-affinity" as well as the "low-affinity" thymidine transport system in a non-competitive manner immediately upon addition. Nicotinoyl-procaine, tetracaine, and dibucaine showed a similar inhibition profile with an inhibition of 10--15% at 50 mumol/l, or of more than 60% at 1 mmol/l. The less-lipophilic procaine showed a distinctly lower inhibition (10% at 1 mmol/l). The inhibitory effect was reversible and not dependent on Ca2+. All local anesthetics exerted identical effects in hepatocytes from young and old rats. Nicotinoyl-procaine and tetracaine inhibited cellular respiration in young and old rats up to a maximum of 50%. Procaine did not reduce O2 consumption below 1 mmol/l. This inhibition appeared also immediately upon addition, was not reversible, and not dependent on Ca2+. It is concluded that local anesthetics impair quite different biological processes like thymidine transport and cellular respiration in hepatocytes from young and old animals even at concentrations below 100 mumol/l. The magnitude of inhibition was correlated to the lipid solubility of the local anesthetics. The mechanism seemed to be different to the anesthetic action and it is supposed that it is a direct hydrophobic interaction with membrane proteins. Thus the local anesthetic-induced increase in membrane fluidity could not improve the age-dependent impairment of thymidine transport. The reduction of respiration is considered to be due to reduced O2 diffusion. This inhibition is in striking contrast to previously observed stimulatory effects which in part lead to the use of local anesthetics in geriatrics.
mesh_terms: D000375:Aging; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003992:Dibucaine / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D009539:Nicotinic Acids / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D011343:Procaine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D013748:Tetracaine / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism*
chemical_list: D000779:Anesthetics, Local; D009539:Nicotinic Acids; D013748:Tetracaine; C020778:nicotinoylprocaine; D011343:Procaine; D003992:Dibucaine; D013936:Thymidine