Adenosine 3':5'-cyclic monophosphate mediates a 5-hydroxytryptamine-induced response in neonatal rat motoneurones.
5-Hydroxytryptamine (5-HT) is present in nerve fibres descending from the brainstem Raphe nuclei to motoneurones and its release is thought to exert excitatory actions. 5-HT, applied from the outside, directly depolarizes spinal and cranial motoneurones in slices. This action of 5-HT is mediated, in part, by an inwardly rectifying cationic current, Ih. In cardiac cells, an equivalent current, if, has been shown to be directly activated by adenosine 3':5'-cyclic monophosphate (cAMP) applied to the inside of the patch membrane. By applying the whole-cell method to thin slices of brainstem and spinal cord, we have shown that intracellularly applied camp and extracellularly applied dibutyryl camp or forskolin mimics the inward current induced by 5-ht. The selective cAMP phosphodiesterase inhibitor, Ro 20-1724, clearly prolonged the 5-HT-induced current. Maximal doses of dibutyryl cAMP or forskolin occluded the 5-HT-induced current. The broad spectrum protein kinase inhibitors 1-(5-isoquinolinesulphonyl)-2-methlypiperazine (H-7) and N-[2-(methylamino)ethyl]-5-isoquinolinesulphonamide (H-8) had no effect on the currents induced by 5-HT and forskolin. From these results, we suggest that activation of 5-HT receptors on the motoneuronal membrane stimulates formation of intracellular cAMP, thereby inducing the inward current, possibly by a direct action on Ih.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001933:Brain Stem / Q000166:cytology / Q000502:physiology; D003994:Bucladesine / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology
D004791:Enzyme Inhibitors; D007473:Ion Channels; D007546:Isoquinolines; D010879:Piperazines; D005576:Colforsin; D002586:Cesium; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D012701:Serotonin; D003994:Bucladesine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases