Cyclic nucleotide potentiation of muscarinic responses in neuroblastoma cells.
The role of cyclic nucleotides in modulating acetylcholine-induced and dopamine-induced responses was examined with cultured neuroblastoma N1E-115 cells by means of intracellular recording techniques. Acetylcholine-induced muscarinic hyperpolarization and muscarinic depolarization were potentiated by bath application of a dibutyryl analog of adenosine 3',5'-phosphate (cyclic AMP) or phosphodiesterase inhibitors, 3-isobutyl-1-methylxanthine and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone. Dibutyryl cyclic AMP did not affect the resting membrane potential and membrane resistance. Acetylcholine-induced nicotinic depolarization was unaffected by dibutyryl cyclic AMP or phosphodiesterase inhibitors. Intracellular pressure injection of cyclic AMP caused a potentiation of muscarinic hyperpolarization and muscarinic depolarization without marked change in the resting membrane potential. Nicotinic depolarization and dopamine depolarization were not affected by cyclic AMP injection. Among the possible metabolites of cyclic AMP, injection of adenosine potentiated muscarinic hyperpolarization, but did not change nicotinic depolarization and dopamine depolarization. Injection of guanosine 3',5'-phosphate (cyclic GMP) potentiated muscarinic hyperpolarization and muscarinic depolarization without effect on nicotinic depolarization and dopamine depolarization. We conclude that cyclic AMP and cyclic GMP enhance muscarinic responses in neuroblastoma cells. It is suggested that synaptic transmission in the nervous system may be modulated postsynaptically by changes in intracellular cyclic nucleotide levels.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000225:Adenine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*
D011976:Receptors, Muscarinic; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; C016276:8-bromocyclic GMP; D003994:Bucladesine; D000242:Cyclic AMP; D006152:Cyclic GMP; D000225:Adenine; D000241:Adenosine; D000109:Acetylcholine; D015056:1-Methyl-3-isobutylxanthine; D004298:Dopamine