Nicotinamide-adenine dinucleotide regulates muscarinic receptor-coupled K+ (M) channels in rodent NG108-15 cells.

AUTOR(ES)

Higashida, H

RESUMO

1. The possible role of nicotinamide-adenine dinucleotide (NAD+) and cyclic adenosine diphosphate ribose (cADPR) as regulators of M-type K+ currents (IK(M)) has been studied in whole-cell patch-clamped NG108-15 mouse neuroblastoma x rat glioma cells that had been transformed to express m1 muscarinic acetylcholine receptors (mAChRs). 2. Pre-incubation of NG108-15 cells for 6-8 h with streptozotocin (2-5 mM) reduced NAD+ levels by 40-50%. Nicotinamide (2-5 mM) increased NAD+ levels and prevented depletion by streptozotocin. 3. Streptozotocin pretreatment reduced the inhibition of IK(M) produced by 100 microM acetylcholine (ACh) from 51.6 +/- 7.0 to 29.1 +/- 7.5%. This was prevented by simultaneous pre-incubation with 2 mM nicotinamide or by adding 2 mM NAD+ to the pipette solution. Neither procedure significantly affected the initial amplitude of IK(M). 4. Inclusion of 2 microM cADPR in the pipette solution induced a slow loss of IK(M) with a time constant of about 20 min. 5. It is concluded that mAChR-induced inhibition of IK(M) requires intracellular NAD+. This might be needed for the formation of cADPR as a regulator or messenger for IK(M) inhibition.

Documentos Relacionados

• Purification of the opiate receptor of NG108-15 neuroblastoma-glioma hybrid cells.
• Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG108-15 cells.
• Electrophysiological consequences of ligand binding to the desensitized 5-HT3 receptor in mammalian NG108-15 cells.
• Ca2+ inhibits guanine nucleotide-activated phospholipase D in neural-derived NG108-15 cells.
• Hyperpolarization of neuroblastoma-glioma hybrid NG108-15 by vanadium ions.