cyclic-gmp and bemesetron

Serotonin (5-HT)-2 receptor-mediated cGMP generation was investigated in comparison with calcium (Ca2+) mobilization in C6 glioma cells. 5-HT enhanced cGMP generation, and risperidone and ketanserin potently blocked the response. These results indicate that 5-HT-2 receptors are responsible for the cGMP generation. 5-HT-induced cGMP production was completely abolished by BAPTA, an intracellular Ca2+ chelating agent, or NG-mono-methyl-L-arginine(NMMA), a nitric oxide synthase (NOS) inhibitor, suggesting that 5-HT-induced cGMP generation was through nitric oxide (NO)-dependent pathway. 5-HT (10 microM)-elicited Ca2+ mobilization and cGMP generation were reduced to 40 and 15% after pretreatment with 10 microM 5-HT for 4 hours. NMMA did not modify 5-HT-induced desensitization of either Ca2+ mobilization or cGMP generation, suggesting that NO pathway is independent of the desensitization. The present study has demonstrated the nature of 5-HT-2 receptor-mediated cGMP generation in C6 glioma cells.

Topics: Animals; Arginine; Calcium; Chelating Agents; Cyclic GMP; Dopamine Antagonists; Edetic Acid; Egtazic Acid; Glioma; Haloperidol; Ketanserin; Nitric Oxide; omega-N-Methylarginine; Rats; Receptors, Serotonin; Risperidone; Serotonin Antagonists; Tropanes; Tumor Cells, Cultured

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

1. The present study investigated the presence of 5-HT3 receptor using 2-methylserotonin (2-Me-5-HT) in the smooth muscle of Mytilus ABRM. 2. 2-Me-5-HT relaxed the acetylcholine-induced contraction in a dose-dependent manner ranging from 10(-6) to 3 x 10(-4) M (pD2 = 5.55 +/- 0.32). 3. 2-Me-5-HT-induced relaxation was antagonized by 3 x 10(-5) M ketanserin in a competitive manner (pA2 = 5.14 +/- 0.1), but not by cypropheptadine, mianserin, MDL 72222 or ICS 205-930 at a concentration of 3 x 10(-5) M. 4. 2-Me-5-HT (3 x 10(-4) M) did not alter the content of cyclic AMP and cyclic GMP in the ABRM. 5. These findings suggested that the 2-Me-5-HT-induced relaxation was mediated through 5-HT2-like receptors and was not linked to cyclic AMP or GMP systems, and, further, that 5-HT3 receptor subtype was not present in the ABRM.

Topics: Acetylcholine; Animals; Bivalvia; Cyclic AMP; Cyclic GMP; Cyproheptadine; Dose-Response Relationship, Drug; Indoles; Ketanserin; Mianserin; Muscle Relaxation; Muscle, Smooth; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Tropanes; Tropisetron