Involvement of endogeneous glutamate in the stimulatory effect of norepinephrine and serotonin on the hypothalamo-pituitary-adrenocortical axis.
The effects of ionotropic glutamate receptor antagonists on the pituitary adrenal responses following injections of norepinephrine (NE) and serotonin (5-HT) receptor agonists into the hypothalamic paraventricular nucleus (PVN) or electrical stimulation of central NE and 5-HT pathways were studied in anesthetized male rats. PVN injections of an alpha(1)-adrenergic receptor agonist or a serotonergic 5-HT(1A) receptor agonist markedly increased both adrenocorticotropin (ACTH) and corticosterone (CS) serum levels. These responses were significantly inhibited by separate pre-injection of the selective non-NMDA and NMDA glutamate receptor subtype antagonists into the PVN in a dose-dependent manner. Electrical stimulation of either the ventral noradrenergic bundle or the dorsal raphe nucleus markedly increased serum ACTH and CS. These responses were also significantly attenuated by pre-injection of the above glutamate ionotropic receptor antagonists in a dose-dependent manner. These results suggest that glutamatergic interneurons in the PVN, acting via non-NMDA and NMDA receptors, may act as an excitatory mechanism in the NE and 5-HT control of hypothalamic ACTH secretagogues.
Feldman
Shaul
S
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital and Hebrew University-Hadassah Medical School, Jerusalem, Israel. dresner@post.tau.ac.il
Weidenfeld
Joseph
J
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D010656:Phenylephrine / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D011810:Quinoxalines / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D017366:Serotonin Receptor Agonists; D010656:Phenylephrine; D012701:Serotonin; D018698:Glutamic Acid; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000324:Adrenocorticotropic Hormone; D014633:Valine; D006854:Hydrocortisone; D009638:Norepinephrine