Monitoring of cyclic GMP during cerebellar microdialysis in freely-moving rats as an index of nitric oxide synthase activity

Vallebuona, Francesco; Raiteri, Maurizio

doi:10.1016/0306-4522(93)90007-3

Cited by 80 publications

(29 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, the basal extracellular level of cyclic GMP course pattern of the in the cerebellum of freely-moving rats was reduced to about 100 (A) and 300 M 20% by administration of the NO synthase inhibitor, N0-nike indicated by the tro-L-arginine (Vallebuona & Raiteri, 1993) whereas, in the lone). Cycit c GMP hippocampus, the maximal inhibition of the basal level of Each point reprecyclic GMP did not exceed 50% (Vallebuona & Raiteri, 1994 mRNA in the rat brain.…”

Section: Statistics and Expression Of Resultsmentioning

confidence: 96%

“…Previous studies showed that monitoring extracellular cyclic GMP during in vivo microdialysis of the cerebellum (Vallebuona & Raiteri, 1993;Luo et al, 1994) or the hippocampus (Vallebuona & Raiteri, 1994; permits the study of the glutamate receptor/NO synthase/cyclic GMP pathway in freely-moving rats. In the present work we investigated the effects of ODQ on cerebellar or hippocampal Brifish Journal of Pharmacology (1996) 119, 590-594 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vivo microdialysis study of a specific inhibitor of soluble guanylyl cyclase on the glutamate receptor/nitric oxide/cyclic GMP pathway

Fedele¹,

Jin

Varnier³

et al. 1996

British J Pharmacology

View full text Add to dashboard Cite

1 Nitric oxide (NO) is known to stimulate soluble guanylyl cyclase, thereby eliciting an elevation of guanosine 3':5'-cyclic monophosphate (cyclic GMP) 2 Intracerebellar administration of ODQ (1-100 giM) via the microdialysis probe inhibited, in a concentration-dependent manner, the basal extracellular level of cyclic GMP. The maximal inhibition, measured after a 20 min perfusion with 100 jgM ODQ, amounted to 80% and persisted unchanged as long as ODQ was perfused. When ODQ was removed from the perfusion stream after 20 min, the levels of cyclic GMP started to recover, suggesting reversibility of guanylyl cyclase inhibition by ODQ.3 The cyclic GMP response evoked in the cerebellum by NMDA (200 gM) or by ax-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA; 100 gM) was largely attenuated by 100 yM ODQ. The pattern of the inhibition curves suggests competition for guanylyl cyclase between ODQ and the NO generated by NMDA or AMPA receptor activation. 4 ODQ (100 ,UM) prevented the elevation of extracellular cyclic GMP levels provoked by intracerebellar infusion of the NO generator S-nitroso-N-acetylpenicillamine (SNAP; 1 mM). The inhibition of the SNAP effect was rapidly relieved when ODQ was removed from the perfusion fluid. However, ODQ (100 giM) was unable to affect the cyclic GMP response elicited by 5 mM SNAP, in keeping with the proposed idea that ODQ binds to the 'NO receptor' in a reversible and competitive manner.5 Infusion of ODQ (10, 100 or 300 jgM) into the hippocampus of freely-moving rats diminished the basal extracellular level of cyclic GMP. The maximal inhibition amounted to 50% and was produced by 100 giM ODQ. 6 The cyclic GMP response observed when 1 mM SNAP was perfused in the hippocampus, similar in percentage terms to that seen in cerebellum, was dramatically reduced during co-infusion of 100,M ODQ. 7 ODQ appears to act in vivo as a selective, reversible and possibly competitive inhibitor of the soluble guanylyl cyclase targeted by NO. This enzyme may generate most (about 80%) of the cyclic GMP found under basal conditions in the extracellular space of the cerebellum. In the hippocampus, about 50% of the basal cyclic GMP does not seem to originate from the ODQ-sensitive soluble guanylyl cyclase.

show abstract

Section: Statistics and Expression Of Resultsmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

In vivo microdialysis study of a specific inhibitor of soluble guanylyl cyclase on the glutamate receptor/nitric oxide/cyclic GMP pathway

Fedele¹,

Jin

Varnier³

et al. 1996

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Previous works showed that extracellular cGMP in dialysates of cerebellum (Vallebuona and Raiteri 1993;Luo et al 1994) and hippocampus (Vallebuona and Raiteri 1994) reflects in vivo activation of NMDA receptors linked to the nitric oxide system.…”

Section: Introductionmentioning

confidence: 99%

D-serine modulates the NMDA receptor/nitric oxide/cGMP pathway in the rat cerebellum during in vivo microdialysis

Fedele

Bisaglia

Raiteri

1996

Naunyn-Schmiedeberg's Arch Pharmacol

Self Cite

View full text Add to dashboard Cite

Several lines of investigation indicate that Dserine may be an endogenous ligand for the glycine site of N-methyl-D-aspartate (NMDA) receptors in some CNS regions. We here studied the in vivo effects of D-serine on the NMDA receptor/nitric oxide/cGMP pathway by monitoring extracellular cGMP in the cerebellum of freely-moving rats subjected to transcerebral microdialysis. Local application of NMDA (200, 500 l M) through the dialysis probe for 20 min evoked transient, concentration-dependent cGMP responses which peaked in the fraction of drug administration, the nucleotide levels returning to basal values after 40 min. The NMDA-induced elevation of the extracellular nucleotide was completely inhibited by the selective receptor channel blocker dizocilpine (MK-801) locally co-perfused at the concentration of 10 l M. The non-competitive antagonist had no effect on its own suggesting that endogenous glutamic acid does not tonically activate NMDA receptors. The effect of 200 l M NMDA was largely attenuated by 30 l M 7-chloro-kynurenic acid and completely abrogated when the concentration of the strychnine-insensitive glycine receptor antagonist was raised to 100 l M. D-serine (300 l M), perfused in the presence of 7-chloro-kynurenate (30 l M), was able to fully restore the NMDA (200 l M)-induced increase of cGMP extracellular levels. On the other hand, the D-amino acid directly potentiated in a concentration-dependent manner (0.3, 1 and 10 mM) the NMDA (200l M)-evoked cGMP production whereas it was inactive on its own. These data show that in vivo the activation of the strychnine-insensitive glycine site is essential for the functioning of the NMDA receptor complex and can be activated by the selective agonist D-serine. They also confirm that cerebellar NMDA receptors do not have their glycine sites saturated.

show abstract

“…LH-RH release is controlled by release of nitric oxide (NO) from NOergic interneurons that release the soluble gas in juxtaposition to the LH-RH terminals (18,19). In the terminals, NO activates guanylyl cyclase, leading to an increase in cyclic guanosine monophosphate (cGMP), cyclooxygenase, resulting in increased concentrations of prostaglandin E 2 (PGE 2 ), and lipoxygenase, leading to increased concentrations of leukotrienes (20)(21)(22)(23). All of these participate in causing the extrusion of the LH-RH secretory granules into the hypophyseal portal vessels for delivery of LH-RH to the pituitary gland, where it causes the release of luteinizing hormone.…”

mentioning

confidence: 99%

Ascorbic acid acts as an inhibitory transmitter in the hypothalamus to inhibit stimulated luteinizing hormone-releasing hormone release by scavenging nitric oxide

Karanth

Yu²,

Walczewska³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Because ascorbic acid (AA) is concentrated in synaptic vesicles containing glutamic acid, we hypothesized that AA might act as a neurotransmitter. Because AA is an antioxidant, it might therefore inhibit nitric oxidergic (NOergic) activation of luteinizing hormonereleasing hormone (LH-RH) release from medial basal hypothalamic explants by chemically reducing NO. Cell membrane depolarization induced by increased potassium concentration [K ؉ ] increased medium concentrations of both AA and LH-RH. An inhibitor of NO synthase (NOS), N G -monomethyl-L-arginine (NMMA), prevented the increase in medium concentrations of AA and LH-RH induced by high [K ؉ ], suggesting that NO mediates release of both AA and LH-RH. Calcium-free medium blocked not only the increase in AA in the medium but also the release of LH-RH. Sodium nitroprusside, which releases NO, stimulated LH-RH release and decreased the concentration of AA in the incubation medium, presumably because the NO released oxidized AA to dehydro-AA. AA (10 ؊5 to 10 ؊3 M) had no effect on basal LH-RH release but completely blocked high [K ؉ ]-and nitroprusside-induced LH-RH release. N-Methyl-D-aspartic acid (NMDA), which mimics the action of the excitatory amino acid neurotransmitter glutamic acid, releases LH-RH by releasing NO. AA (10 ؊5 to 10 ؊3 M) inhibited the LH-RH-releasing action of NMDA. AA may be an inhibitory neurotransmitter that blocks NOergic stimulation of LH-RH release by chemically reducing the NO released by the NOergic neurons.is present in high concentrations in the hypothalamus (1-3) but its role in the modulation of hypothalamic hormone release is obscure. The brain accumulates AA from the blood and maintains a relatively high concentration (1.1-1.7 mM), independent of AA ingestion (4-7). Neuronal intracellular AA concentrations are 10 times greater than extracellular AA concentration (6, 7). Neuronal activity was shown to increase extracellular AA in vitro (6,(8)(9)(10)(11)(12) and in vivo as determined by voltametry (13). AA is further concentrated in isolated nerve terminals (14). Synaptic vesicles concentrate AA by active transport (15). AA is present in high concentrations in synaptic vesicles of glutamergic neurons (13) and in adrenal medullary catecholamine secretory granules (16,17).The presence of high concentrations of AA in synaptic vesicles and the evidence that it could be released into the extracellular space by neuronal activity suggested to us that AA might be a neurotransmitter. Since high concentrations of AA are already known to be present in the hypothalamus, we hypothesized that AA might control luteinizing hormone-releasing hormone (LH-RH) release, possibly by its antioxidant properties. LH-RH release is controlled by release of nitric oxide (NO) from NOergic interneurons that release the soluble gas in juxtaposition to the LH-RH terminals (18,19). In the terminals, NO activates guanylyl cyclase, leading to an increase in cyclic guanosine monophosphate (cGMP), cyclooxygenase, resulting in increased concentrations of prostagla...

show abstract

Monitoring of cyclic GMP during cerebellar microdialysis in freely-moving rats as an index of nitric oxide synthase activity

Cited by 80 publications

References 25 publications

In vivo microdialysis study of a specific inhibitor of soluble guanylyl cyclase on the glutamate receptor/nitric oxide/cyclic GMP pathway

In vivo microdialysis study of a specific inhibitor of soluble guanylyl cyclase on the glutamate receptor/nitric oxide/cyclic GMP pathway

D-serine modulates the NMDA receptor/nitric oxide/cGMP pathway in the rat cerebellum during in vivo microdialysis

Ascorbic acid acts as an inhibitory transmitter in the hypothalamus to inhibit stimulated luteinizing hormone-releasing hormone release by scavenging nitric oxide

Contact Info

Product

Resources

About