title: Stimulation of 5-HT1A receptor inhibits apoptosis induced by serum deprivation in cultured neurons from chick embryo.
abstract: Primary cultures of neurons from chick embryo telencephalons were deprived of serum to induce apoptotic cell death. After 24 h of serum withdrawal, we found a reduction in cell viability from 85% to 72% and an increase in the number of apoptotic cells from 12% to 29%. The 5-HT1A receptor agonist 8-OH-DPAT inhibited the decrease in cell viability and reduced the number of apoptotic cells in a concentration-dependent manner. The anti-apoptotic effect of 8-OH-DPAT (1 microM) could be blocked by adding the selective 5-HT1A antagonist MPPI (10 microM), but not in the presence of the dopamine receptor antagonist chlorpromazine (1 microM) and of the beta-receptor blocker propranolol (10 microM). In addition, anti-nerve growth factor (NGF) antibodies inhibited the protective effect of 8-OH-DPAT, suggesting that induction of NGF was involved in the mechanism of action. Serum deprivation alone already induced a release of NGF (10 pg/flask) which protected the neurons from further cell death. Accordingly, the addition of the same amount of exogenous NGF restored cell viability up to control level and addition of anti-NGF antibodies further decreased cell viability to 56%. In the presence of 8-OH-DPAT (1 microM), the level of NGF in the culture medium was only slightly yet consistently increased compared to serum deprivation from 4 h onwards. Thus, our data suggest that the anti-apoptotic effect of 8-OH-DPAT is mediated by the stimulation of 5-HT1A receptors. Furthermore, the induction of neuronal NGF synthesis and secretion contributes to its neuroprotective action.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Fachbereich Pharmazie der Philipps-Universität Marburg, Germany. ahlemeye@mailer.uni-marburg.de
authors.forename: B
authors.initials: B
authors.lastname: Ahlemeyer
authors.forename: J
authors.initials: J
authors.lastname: Krieglstein
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D002746:Chlorpromazine / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013687:Telencephalon / Q000166:cytology
chemical_list: D000319:Adrenergic beta-Antagonists; D000631:Aminopyridines; D016895:Culture Media, Serum-Free; D018492:Dopamine Antagonists; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011433:Propranolol; D002746:Chlorpromazine