Modulation of in vivo striatal transmitter release by nitric oxide and cyclic GMP.
The effects of nitric oxide (NO) and cyclic GMP on in vivo transmitter release in the rat striatum were investigated using microdialysis sampling in urethane-anaesthetised animals. The NO release-inducing substances S-nitrosoacetylpenicillamine (SNAP), S-nitrosoglutathione (SNOG), and sodium nitroprusside (SNP) increased extracellular concentrations of aspartate (Asp), glutamate (Glu), gamma-aminobutyric acid (GABA), taurine (Tau), acetylcholine (ACh), and serotonin (5-HT). Dopamine (DA) concentrations were decreased by SNAP but were increased by SNOG and SNP. An NO scavenger, haemoglobin, blocked or reduced the effects of SNAP on transmitter release. However, the control carrier compounds for SNAP, SNOG, and SNAP (penicillamine, glutathione, and potassium ferricyanide, respectively, which do not induce release of NO) also increased GABA, Tau, DA, and 5-HT concentrations. When NO gas was given directly by dissolving it in degassed Ringer's solution, DA concentrations decreased significantly, and those of Asp, Glu, GABA, Tau, ACh, and 5-HT increased. These effects of NO gas were all inhibited by coadministration of haemoglobin and for GABA, Tau, ACh, and DA showed some calcium dependency. The cyclic GMP agonists 8-bromo-cyclic GMP and dibutryl-cyclic GMP stimulated dose-dependent increases in Asp, Glu, GABA, Tau, ACh, DA, and 5-HT concentrations. Increased striatal transmitter release in response to NO may therefore be mediated by its stimulatory action on cyclic GMP formation. NO inhibition of DA release may be mediated indirectly through its stimulation of local cholinergic and GABAergic neurones.
Guevara-Guzman
R
R
Department of Neurobiology, AFRC Babraham Institute, Cambridge, England, UK.
Emson
P C
PC
Kendrick
K M
KM
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D006152:Cyclic GMP / Q000502:physiology*; D005740:Gases / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology; D051381:Rats
D005740:Gases; D018377:Neurotransmitter Agents; D009569:Nitric Oxide; D006152:Cyclic GMP