Cyclic GMP generation mediated by 5-HT-2 receptors via nitric oxide-dependent pathway and its effect on the desensitization of 5-HT-2 receptors in C6 glioma cells.
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.
Kagaya
A
A
Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Japan.
Motohashi
N
N
Kugaya
A
A
Yamaji
T
T
Hayashi
T
T
Okamoto
Y
Y
Shinno
H
H
Takebayashi
M
M
Uchitomi
Y
Y
Yamawaki
S
S
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005910:Glioma; D006220:Haloperidol / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology*; D018967:Risperidone / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014326:Tropanes / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019323:omega-N-Methylarginine
D002614:Chelating Agents; D018492:Dopamine Antagonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004533:Egtazic Acid; D001120:Arginine; D007650:Ketanserin; D004492:Edetic Acid; D006152:Cyclic GMP; D006220:Haloperidol; D018967:Risperidone; C042253:bemesetron; D002118:Calcium