Inhibition of nicotinic acetylcholine receptors by bis (2,2,6,6-tetramethyl- 4-piperidinyl) sebacate (Tinuvin 770), an additive to medical plastics.

R L Papke, A G Craig, S F Heinemann

Index: J. Pharmacol. Exp. Ther. 268(2) , 718-26, (1994)

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Abstract

Bis (2,2,6,6-tetramethyl-4-piperidinyl) sebacate (BTMPS; Tinuvin 770), a sterically hindered amine light and radiation stabilizer manufactured by Ciba-Geigy Corp. (Summit, NJ) and used in a wide range of plastics, inhibits nicotinic acetylcholine receptors expressed in Xenopus oocytes in a use-dependent manner. BTMPS is a symmetrical conjugate of methylated piperidines, which are themselves effective inhibitors, but have faster kinetics of inhibition and recovery than BTMPS. The time constants for the recovery from inhibition by BTMPS are on the order of 1 to 4 hr for neuronal nicotinic receptor subunit combinations. Muscle-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 incorporate neuronal beta-subunits (alpha 1-, beta 2- gamma and delta- and alpha-1-, beta 4- and gamma-delta), are blocked in a less reversible fashion than are normal muscle-type receptors, suggesting that there is an interaction between BTMPS and the neuronal acetylcholine receptor beta-subunits. Glutamate receptors are not inhibited by BTMPS. Certain plastic syringes release BTMPS, and agonist solutions exposed to these syringes also cause use-dependent inhibition of nicotinic receptors. Erroneous interpretation of data regarding nicotinic receptors may result from the use of plastics releasing BTMPS.