nitroarginine and bemesetron

Long-term depression (LTD) is a use-dependent decrease in synaptic efficacy widely recognized as a form of synaptic plasticity related to cognitive function in the central nervous system. Such response has previously not been demonstrated in autonomic ganglia. In the isolated superior cervical ganglion (SCG) of the rat (superfused with Locke solution containing 100 microM choline), low-frequency stimulation (LFS, 3-5 Hz/15 min) of the preganglionic nerve produced a long-lasting (up to 3 h ), significant (20-40%) decrease in the amplitude of the extracellularly recorded postganglionic compound action potential. Pretreatment of ganglia with the 5-HT(3) receptor antagonist tropisetron (0.5 microM) completely prevented the induction of ganglionic LTD (gLTD). Treatment of ganglia with the 5-HT(3) receptor antagonist MDL 72222 (0.5 microM) during the maintenance phase of established gLTD (1 h after LFS) antagonized the LFS-induced depression. Inhibition of nitric oxide (NO) synthase with l-NOARG (20-50 microM), applied before or after LFS, failed to affect the expression of gLTD. Additionally, pretreatment with the protein synthesis inhibitor emetine (1 microM) totally prevented the expression of gLTD. However, inhibition of protein phosphatase with cantharidin (30 microM) did not interfere with the expression of gLTD. These results indicate the presence of LTD in the rat SCG and suggest that expression of gLTD involves activation of 5-HT(3) receptor.

Topics: Action Potentials; Animals; Autonomic Fibers, Preganglionic; Electric Stimulation; Emetine; Enzyme Inhibitors; Indoles; Male; Nerve Tissue Proteins; Neuronal Plasticity; Nitric Oxide; Nitric Oxide Synthase Type I; Nitroarginine; Phosphoprotein Phosphatases; Protein Synthesis Inhibitors; Rats; Rats, Sprague-Dawley; Serotonin Antagonists; Superior Cervical Ganglion; Tropanes; Tropisetron

The neuronal pathway that initiates nitric oxide-mediated descending relaxation in rat ileum was studied. The descending relaxation, which was suggested to be mediated by nitric oxide from our previous study, was selectively inhibited by 5-HT3 receptor antagonists. It was also inhibited by a nicotinic acetylcholine receptor antagonist. Exogenous 5-hydroxytryptamine (5-HT) and a selective 5-HT3 receptor agonist induced dose-dependent relaxation of ileal circular muscle. 5-HT-induced relaxation was selectively inhibited by 5-HT3 receptor antagonists. Nicotine also induced relaxation of the circular muscle, and its effect was inhibited by 5-HT3 receptor antagonists. 5-HT and nicotine increased the cyclic GMP content of the ileal tissue. Nitro-L-arginine inhibited the increases induced by both compounds in the cyclic GMP content, and a 5-HT3 receptor antagonist also inhibited that induced by nicotine. These results indicate that activation of a cholinergic neuron-5-HT neuron pathway initiates nitric oxide-mediated descending relaxation in rat ileum.

Topics: Animals; Arginine; Cholinergic Antagonists; Cyclic GMP; Dose-Response Relationship, Drug; Ileum; Indoles; Male; Muscle Relaxation; Muscle, Smooth; Nicotine; Nitric Oxide; Nitroarginine; Rats; Rats, Wistar; Receptors, Cholinergic; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Tropanes; Tropisetron