Heterologous sensitization of adenylate cyclase activity by serotonin in the rat cerebral cortex - PubMed (original) (raw)
Heterologous sensitization of adenylate cyclase activity by serotonin in the rat cerebral cortex
A C Rovescalli et al. Eur Neuropsychopharmacol. 1993 Dec.
Abstract
In vitro exposure of rat cerebrocortical slices to microM concentrations of serotonin (5HT) results in an increased response of adenylate cyclase to isoproterenol (ISO). No change in the affinity of the beta-adrenoceptor toward the agonist was found after 5HT exposure when measuring ISO displacement of [3H]CGP 12177 binding. A similar increase of adenylate cyclase response was also found when using VIP as a stimulatory agent. The dose-response curve of adenylate cyclase to the GTP analogue, GppNHp, was modified by 5HT, which promotes a significantly higher maximal response without altering the potency of GppNHp. Forskolin-stimulated adenylate cyclase activity was not affected by 5HT. Serotonergic 5HT2 receptors are involved in the sensitization of adenylate cyclase to GppNHp, since the selective 5HT2 antagonist ketanserin inhibits the effect of 5HT, whereas the 5HT2 agonist DOI mimics 5HT. The involvement of 5HT2 receptor-coupled activation of protein kinase C is also demonstrated: direct protein kinase C activators such as phorbol esters and s,n-dioctanoylglycerol behave in the same manner as 5HT, while the protein kinase C inhibitor CGP 41251 prevents 5HT from increasing adenylate cyclase responsiveness to GppNHp. Moreover, in vitro exposure of cortical slices to 5HT results in reduced inhibition of adenylate cyclase by somatostatin. Since no change was observed at the receptor level and in the direct stimulation of the catalytic subunit of the enzyme, we propose that 5HT might accomplish the sensitization of adenylate cyclase through protein kinase C by inactivating the inhibitory coupling protein Gi and facilitating the interaction of the exogenous GppNHp with the stimulatory coupling protein Gs.
Similar articles
- Protein kinase C stimulates adenylate cyclase activity in prolactin-secreting rat adenoma (GH4C1) pituicytes by inactivating the inhibitory GTP-binding protein Gi.
Gordeladze JO, Björo T, Torjesen PA, Ostberg BC, Haug E, Gautvik KM. Gordeladze JO, et al. Eur J Biochem. 1989 Aug 1;183(2):397-406. doi: 10.1111/j.1432-1033.1989.tb14941.x. Eur J Biochem. 1989. PMID: 2569396 - Phorbol ester regulates stimulatory and inhibitory pathways of the hormone-sensitive adenylate cyclase system in rat reticulocytes.
Yamashita A, Kurokawa T, Une Y, Ishibashi S. Yamashita A, et al. Eur J Pharmacol. 1988 Jul 7;151(2):167-75. doi: 10.1016/0014-2999(88)90797-2. Eur J Pharmacol. 1988. PMID: 2844550 - New perspectives on the molecular pharmacology of affective disorders.
Sulser F. Sulser F. Eur Arch Psychiatry Neurol Sci. 1989;238(5-6):231-9. doi: 10.1007/BF00449803. Eur Arch Psychiatry Neurol Sci. 1989. PMID: 2548868 Review. - The role of serotonin in cardiovascular diseases and their treatment.
van Zwieten PA, Blauw GJ, van Brummelen P. van Zwieten PA, et al. Cardiovasc Drugs Ther. 1990 Dec;4(6):1443-7. doi: 10.1007/BF02026489. Cardiovasc Drugs Ther. 1990. PMID: 2081137 Review.
Cited by
- Organophosphate insecticides target the serotonergic system in developing rat brain regions: disparate effects of diazinon and parathion at doses spanning the threshold for cholinesterase inhibition.
Slotkin TA, Tate CA, Ryde IT, Levin ED, Seidler FJ. Slotkin TA, et al. Environ Health Perspect. 2006 Oct;114(10):1542-6. doi: 10.1289/ehp.9337. Environ Health Perspect. 2006. PMID: 17035140 Free PMC article. - Mitral cell beta1 and 5-HT2A receptor colocalization and cAMP coregulation: a new model of norepinephrine-induced learning in the olfactory bulb.
Yuan Q, Harley CW, McLean JH. Yuan Q, et al. Learn Mem. 2003 Jan-Feb;10(1):5-15. doi: 10.1101/lm.54803. Learn Mem. 2003. PMID: 12551959 Free PMC article. - Serotonergic systems targeted by developmental exposure to chlorpyrifos: effects during different critical periods.
Aldridge JE, Seidler FJ, Meyer A, Thillai I, Slotkin TA. Aldridge JE, et al. Environ Health Perspect. 2003 Nov;111(14):1736-43. doi: 10.1289/ehp.6489. Environ Health Perspect. 2003. PMID: 14594624 Free PMC article. - Developmental neurotoxicity of low dose diazinon exposure of neonatal rats: effects on serotonin systems in adolescence and adulthood.
Slotkin TA, Ryde IT, Levin ED, Seidler FJ. Slotkin TA, et al. Brain Res Bull. 2008 Mar 28;75(5):640-7. doi: 10.1016/j.brainresbull.2007.10.008. Epub 2007 Nov 12. Brain Res Bull. 2008. PMID: 18355640 Free PMC article.