Nitric oxide- and cGMP-active compounds affect the discharge of substantia nigra pars reticulata neurons: in vivo evidences in the rat.
The nitric oxide (NO)-active drugs influence on the bioelectric activity of neurons of the pars reticulata of the substantia nigra was studied in urethane-anesthetized rats. A first group of animals was treated with 7-nitro-indazole (7-NI), a preferential inhibitor of neuronal NO synthase. In a second group of rats, electrophysiological recordings were coupled with microiontophoretic administration of Nomega-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor), 3-morpholino-sydnonimin-hydrocloride (SIN-1, a NO donor) and 8-Br-cGMP (a cell-permeable analogue of cGMP, the main second-messenger of NO neurotransmission). 7-NI and L-NAME caused a statistically significant decrease in the firing rate of most of the responsive cells, while application of SIN-1 and 8-Br-CGMP induced statistically significant excitatory effects. The results suggest a NO mediated excitatory modulation of the SNr neurons activity with a possible involvement of the cGMP pathway.
Dipartimento di Medicina Sperimentale, Sezione di Fisiologia umana G. Pagano, Università degli Studi di Palermo, Palermo, Italy.
Fabio
F
Carletti
Giuseppe
G
Ferraro
Valerio
V
Rizzo
Stefania
S
D'Agostino
Gioacchino
G
Lonobile
Pierangelo
P
Sardo
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007478:Iontophoresis; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D052248:Nitric Oxide Synthase Type I; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester