Effects of nitric oxide-active drugs on the discharge of subthalamic neurons: microiontophoretic evidence in the rat.
The presence of nitric oxide (NO) synthase and of soluble guanylyl cyclase, the main NO-activated metabolic pathway, has been demonstrated in many cells of the subthalamic nucleus. In this study, the effects induced on the firing of 96 subthalamic neurons by microiontophoretically administering drugs modifying NO neurotransmission were explored in anaesthetized rats. Recorded neurons were classified into regularly and irregularly discharging on the basis of their firing pattern. Nomega-nitro-L-arginine methyl ester (L-NAME; a NO synthase inhibitor), 3-morpholino-sydnonimin-hydrocloride (SIN-1; a NO donor), S-nitroso-glutathione (SNOG; another NO donor) and 8-Br-cGMP (a cell-permeable analogue of cGMP, the main second-messenger of NO neurotransmission) were iontophoretically applied while performing single-unit extracellular recordings. The activity of most neurons was influenced in a statistically significant way: in particular, both current-related inhibitory L-NAME-induced effects (20/39 tested cells) and excitatory effects of SIN-1 (25/41 tested neurons), SNOG (19/32 tested cells) and 8-Br-cGMP (13/19 tested neurons) were demonstrated. Neither statistically significant differences between the responses of regularly and irregularly discharging cells, nor specific topographical clustering of responding neurons, were demonstrated. Neurons administered drugs oppositely modulating the NO neurotransmission often displayed responses to only one treatment. We hypothesize that NO neurotransmission could exert a modulatory influence upon subthalamic neurons, with a prevalent excitatory effect. However, in the light of the presence of some responses of opposite sign to the same drug displayed by different subthalamic neurons, more complex effects of NO neurotransmission could be suggested, probably due to interactions with other classical neurotransmitter systems.
Sardo
Pierangelo
P
Dipartimento di Medicina Sperimentale, Sezione di Fisiologia umana, Università degli Studi di Palermo, Corso Tukory, 129-90134 Palermo, Italy. pierangelo.sardo@unipa.it
Carletti
Fabio
F
D'Agostino
Stefania
S
Rizzo
Valerio
V
Ferraro
Giuseppe
G
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007478:Iontophoresis / Q000379:methods; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D020531:Subthalamic Nucleus / Q000166:cytology*; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D013873:Thionucleotides; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; C002385:linsidomine; D008981:Molsidomine; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester