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Nitric oxide-evoked glutamate release and cGMP production in cerebellar slices: Control by presynaptic 5-HT1D receptors
- Source :
-
Neurochemistry International . Jul2006, Vol. 49 Issue 1, p12-19. 8p. - Publication Year :
- 2006
-
Abstract
- Abstract: We previously reported that pre- and postsynaptic 5-hydroxytryptamine (5-HT) receptors effectively control glutamatergic transmission in adult rat cerebellum. To investigate where 5-HT acts in the glutamate ionotropic receptors/nitric oxide/guanosine 3′,5′-cyclic monophosphate (cGMP) pathway, in the present study 5-HT modulation of the cGMP response to the nitric oxide donor S-nitroso-penicillamine (SNAP) was studied in adult rat cerebellar slices. While cGMP elevation produced by high-micromolar SNAP was insensitive to 5-HT, 1μM SNAP, expected to release nitric oxide in the low-nanomolar concentration range, elicited cGMP production and endogenous glutamate release both of which could be prevented by activating presynaptic 5-HT1D receptors. Released nitric oxide appeared responsible for cGMP production and glutamate release evoked by 1μM SNAP, as both the effects were mimicked by the structurally unrelated nitric oxide donor 2-(N,N-diethylamino)-diazenolate-2-oxide (0.1μM). Dependency of the 1μM SNAP-evoked release of glutamate on external Ca2+, sensitivity to presynaptic release-regulating receptors and dependency on ionotropic glutamate receptor functioning, suggest that nitric oxide stimulates exocytotic-like, activity-dependent glutamate release. Activation of ionotropic glutamate receptors/nitric oxide synthase/guanylyl cyclase pathway by endogenously released glutamate was involved in the cGMP response to 1μM SNAP, as blockade of NMDA/non-NMDA receptors, nitric oxide synthase or guanylyl cyclase, abolished the cGMP response. To conclude, in adult rat cerebellar slices low-nanomolar exogenous nitric oxide could facilitate glutamate exocytotic-like release possibly from parallel fibers that subsequently activated the glutamate ionotropic receptors/nitric oxide/cGMP pathway. Presynaptic 5-HT1D receptors could regulate the nitric oxide-evoked release of glutamate and subsequent cGMP production. [Copyright &y& Elsevier]
- Subjects :
- *NITRIC oxide
*PRESYNAPTIC receptors
*LABORATORY rats
*NEUROPHYSIOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 01970186
- Volume :
- 49
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Neurochemistry International
- Publication Type :
- Academic Journal
- Accession number :
- 20820207
- Full Text :
- https://doi.org/10.1016/j.neuint.2005.12.010