Ionotropic histamine receptors and H-2 receptors modulate supraoptic oxytocin neuronal excitability and dye coupling

Citation
Gi. Hatton et Qz. Yang, Ionotropic histamine receptors and H-2 receptors modulate supraoptic oxytocin neuronal excitability and dye coupling, J NEUROSC, 21(9), 2001, pp. 2974-2982
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
21
Issue
9
Year of publication
2001
Pages
2974 - 2982
Database
ISI
SICI code
0270-6474(20010501)21:9<2974:IHRAHR>2.0.ZU;2-R
Abstract
Histaminergic neurons of the tuberomammillary nucleus (TM) project monosyna ptically to the supraoptic nucleus (SON). This projection remains intact in our hypothalamic slices and permits investigation of both brief synaptic r esponses and the effects of repetitively activating this pathway. SON oxyto cin (OX) neurons respond to single TM stimuli with fast IPSPs, whose kineti cs resemble those of GABA(A) or glycine receptors. IPSPs were blocked by th e Cl- channel blocker picrotoxin, but not by bicuculline or strychnine, and by histamine H-2, but not by H-1 or H-3 receptor antagonists, suggesting t he presence of an ionotropic histamine receptor and the possible nonspecifi city of currently used H-2 antagonists. G-protein mediation of the IPSPs wa s ruled out using guanosine 5'-O-(2-thiodiphosphate) (GDP-betaS), pertussis toxin, and Rp-adenosine 3',5'-cyclic monophosphothioate triethylamine (Rp- cAMPs), none of which blocked evoked IPSPs. We also investigated the effect s of synaptically released histamine on dye coupling and neuronal excitabil ity. One hundred seventy-three OX neurons were Lucifer yellow-injected in h orizontal slices. Repetitive TM stimulation (10 Hz, 5-10 min) reduced coupl ing, an effect blocked by H-2, but not by H-1 or H-3, receptor antagonists. Because H-2 receptors are linked to activation of adenylyl cyclase, TM-sti mulated reduction in coupling was blocked by GDP-betaS, pertussis toxin, an d Rp-cAMPs and was mimicked by 8-bromo-cAMP, 3-isobutyl-1-methylxanthine, a nd Sp-cAMP. Membrane potentials of OX and vasopressin neurons were hyperpol arized, accompanied by decreased conductances, in response to bath applicat ion of 8-bromo-cAMP but not the membrane-impermeable cAMP. These results su ggest that synaptically released histamine, in addition to evoking fast IPS Ps in OX cells, mediates a prolonged decrease in excitability and uncouplin g of the neurons.