Somatostatin inhibits glutamate release from mouse cerebrocortical nerve endings through presynaptic sst2 receptors linked to the adenylyl cyclase-protein kinase A pathway.
The effects of somatostatin ( SRIF, somatotropin release inhibiting factor) on the release of glutamate have been investigated using superfused mouse cerebrocortical synaptosomes. SRIF-14 inhibited the K+ (12 mM)-evoked overflow of preaccumulated [3H]D-aspartate as well as that of endogenous glutamate. Cyanamid 154806, a selective sst2 receptor antagonist, but not BIM-23056, an antagonist at sst5 receptors, prevented the SRIF-14 effect. Octreotide and L779976, selective agonists at sst2 receptors, mimicked SRIF-14, whereas L797591, L796778, L803087 and L362855, selective agonists at sst1, sst3, sst4 and sst5 receptor subtypes, were inactive. Activation of sst2 receptors seems to involve inhibition of the adenylyl cyclase-protein kinase A pathway present in glutamatergic terminals since the adenylyl cyclase inhibitor MDL-12,330A and the protein kinase A inhibitor H89 prevented the K+-evoked [3H]D-aspartate overflow. Consistent with the involvement of adenylyl cyclase, depolarization with 12 mM K+ increased synaptosomal cyclic AMP (cAMP) content, while forskolin, an adenylyl cyclase activator, potentiated basal [3H]D-aspartate release in an octreotide-, MDL-12,330A- and H89-sensitive manner. To conclude, glutamatergic cerebrocortical nerve endings possess release-inhibiting sst2 receptors which represent potential targets for new drugs able to mitigate the effects of excessive glutamate transmission.[1]References
- Somatostatin inhibits glutamate release from mouse cerebrocortical nerve endings through presynaptic sst2 receptors linked to the adenylyl cyclase-protein kinase A pathway. Grilli, M., Raiteri, L., Pittaluga, A. Neuropharmacology (2004) [Pubmed]
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