Interactions Between Tachykinins And Diverse Human Nicotinic Acetylcholine Receptor Subtypes
Nicotinic acetylcholine receptors (nAChR) are diverse members of the ligand-gated ion channel superfamily of neurotransmitter receptors and play critical roles in chemical signaling throughout the nervous system. Reports of effects of substance P (SP) on nAChR function prompted us to investigate interactions between several tachykinins and human nAChR subtypes using clonal cell lines as simple experimental models. Acute exposure to SP inhibits carbamylcholine- or nicotine-stimulated function measured using 86Rb + efflux assays of human ganglionic (Î±3Î²4) nAChR expressed in SH- SY5Y neuroblastoma cells (IC 50 ~ 2.3 Î¼M) or of human muscle-type (Î±1Î²1Î³Î´) nAChR expressed in TE671/RD clonal cells (IC 50 ~ 21 Î¼M). SP also acutely blocks function of rat ganglionic nAChR expressed in PC12 pheochromocytoma cells (IC 50 ~ 2.1 Î¼M). Neurokinin A and eledoisin inhibit function (extrapolated IC 50 values between 60 and 160 Î¼M) of human muscle-type or ganglionic nAChR, but neurokinin B does not, and neither human nAChR is as sensitive as PC12 cell Î±3Î²4-nAChR to eledoisin or neurokinin A inhibition. At concentrations that produce blockade of nAChR function, SP fails to affect binding of [ 3H]acetylcholine to human muscle-type or ganglionic nAChR. SP-mediated blockade of rat or human ganglionic nAChR function is insurmountable by increasing agonist concentrations. Collectively, these results indicate that tachykinins act noncompetitively to inhibit human nAChR function with potencies that vary across tachykinins and nAChR subtypes. They also indicate that tachykinin actions at nAChR could further contribute to complex cross-talk between nicotinic cholinergic and tachykinin signals in regulation of nervous system activity.
Digital Object Identifier (DOI)
Lukas, Ronald J. and Eisenhour, Cynthia M., "Interactions Between Tachykinins And Diverse Human Nicotinic Acetylcholine Receptor Subtypes" (1996). Neurobiology. 235.