INHIBITION OF NICOTINIC ACETYLCHOLINE-RECEPTORS BY BIS (2,2,6,6-TETRAMETHYL-4-PIPERIDINYL) SEBACATE (TINUVIN-770), AN ADDITIVE TO MEDICAL PLASTICS

Bis (2,2,6,6-tetramethyl-4-piperidinyl) sebacate (BTMPS; Tinuvin 770), a sterically hindered amine light and radiation stabilizer manufactur ed by Ciba-Geigy Corp, (Summit, NJ) and used in a wide range of plasti cs, inhibits nicotinic acetylcholine receptors expressed in Xenopus oo cytes in a use-dependent manner. BTMPS is a symmetrical conjugate of m ethylated piperidines, which are themselves effective inhibitors, but have faster kinetics of inhibition and recovery than BTMPS. The time c onstants for the recovery from inhibition by BTMPS are on the order of 1 to 4 hr for neuronal nicotinic receptor subunit combinations. Muscl e-type receptors (alpha 1-, beta 1- gamma and delta-subunits) are also inhibited by BTMPS, but with full control responses recovered after a 5-min wash. Hybrids of muscle and neuronal subunits, which incorporat e neuronal P-subunits (alpha 1-, beta 2- gamma and delta- and alpha-1- , beta 4- and gamma-delta), are blocked in a less reversible fashion t han are normal muscle-type receptors, suggesting that there is an inte raction between BTMPS and the neuronal acetylcholine receptor beta-sub units. Glutamate receptors are not inhibited by BTMPS. Certain plastic syringes release BTMPS, and agonist solutions exposed to these syring es also cause use-dependent inhibition of nicotinic receptors. Erroneo us interpretation of data regarding nicotinic receptors may result fro m the use of plastics releasing BTMPS.