PlumX Metrics
Embed PlumX Metrics

Somatostatin-Induced Activation and Up-Regulation of N -Methyl- d -aspartate Receptor Function: Mediation through Calmodulin-Dependent Protein Kinase II, Phospholipase C, Protein Kinase C, and Tyrosine Kinase in Hippocampal Noradrenergic Nerve Endings

The Journal of Pharmacology and Experimental Therapeutics, ISSN: 0022-3565, Vol: 313, Issue: 1, Page: 242-249
2005
  • 45
    Citations
  • 0
    Usage
  • 18
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

Somatostatin receptors and glutamate N -methyl- d -aspartate (NMDA) receptors coexist on hippocampal noradrenergic axon terminals. Activation of somatostatin receptors was previously found to positively influence the function of NMDA receptors regulating norepinephrine release. The somatostatin receptors involved were pharmacologically characterized as sst5 type in experiments in Mg 2+ -free solutions. Here, we first confirm the pharmacology of these receptors using selective sst5 ligands in Mg 2+ -containing solutions. Moreover, we show by Western blot that the sst5 protein exists on purified hippocampal synaptosomal membranes. We then investigated the pathways connecting the two receptors using as a functional response the release of norepinephrine from rat hippocampal synaptosomes in superfusion. The release of norepinephrine evoked by somatostatin-14 plus NMDA/glycine was partly prevented by the protein kinase C inhibitor GF109203X [dihydrochloride3-[1-[3-(dimethylamino)propyl]-1 H -indol-3-yl]-4-(1 H -indol-3-yl)-1 H -pyrrole-2,5-dione] and by the nonreceptor tyrosine kinase (Src) inhibitors PP2 [3-(4-chlorophenyl)1-(1,1-dimethylethyl)-1 H -pyrazolo[3,4- d ]pyrimidin-4-amine] and lavendustin A; it was largely and almost totally abolished by the phospholipase C inhibitor U73122 [1-(6-[([17β]-3-methoxyextra-1,3,5[10]-trien-17-yl)amino]hexyl)-1 H -pyrrole-2,5-dione] and by the Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93 [ N -(2-[ N -[4-chlorocinnamyl]- N -methyl-amino-methyl]phenyl)- N -(2-hydroxyethyl)-4-methoxy-benzene-sulfonamide-phosphate salt], respectively; and it was unaffected by the protein kinase A inhibitor H89 [ N -(2-[ p -bromocinnamylamino]ethyl)5-isoquinolinesulfonamide hydrochloride]. The norepinephrine release evoked by somatostatin-14/NMDA/glycine was inhibited when anti-phosphotyrosine antibodies had been entrapped into synaptosomes. Entrapping the recombinant activated tyrosine kinase pp60 c-Src strongly potentiated the release of norepinephrine elicited by NMDA/glycine in Mg 2+ -free medium but failed to permit NMDA receptor activation in presence of external Mg 2+ ions. The results suggest the involvement of CaMKII in the sst5 receptor-mediated activation of NMDA receptors in presence of Mg 2+ and of the PLC/PKC/Src pathway in the up-regulation of the ongoing NMDA receptor activity.

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know