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Somatostatinpotentiates NMDAreceptor function viaactivation of InsP3receptors and PKCleading to removal ofthe Mg2+ block… Anna PittalugaAndrea BonfantiMaurizio Raiteri2000 год

Somatostatin potentiates NMDA receptor function via activation of InsP3 receptors and PKC leading to removal of the Mg2+ block without depolarization
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Аннотация: N‐methyl‐ D ‐aspartate (NMDA) receptors exist on noradrenergic axon terminals and mediate enhancement of noradrenaline (NA) release. We here investigated modulation by somatostatin (SRIF, somatotropin release inhibiting factor) of the NMDA‐induced release of NA using superfused hippocampal synaptosomes. The NMDA response was increased by SRIF‐28 and SRIF‐14, but not SRIF‐28 (1–14) , whereas the release of [ 3 H]‐NA elicited by α‐amino‐3‐hydroxy‐5‐methylisoxazide‐4‐propionic acid (AMPA) was unaffected. SRIF‐14 did not mimic glycine at the NMDA receptor but activated SRIF receptors sited on noradrenergic terminals. The SRIF‐14 effect was blocked by pertussis toxin but mimicked by mastoparan, a G‐protein activator. BIM‐23056, but not Cyanamid 154806, antagonized the SRIF‐14 effect. This effect was mimicked by L362855, a partial agonist at the sst 5 subtype, but not by the new selective sst 1 –sst 4 receptor agonists L797591, L779976, L796778 and L803087. Protein kinase C (PKC) inhibitors (H7, staurosporine, GF 209103X, cheleritrine and sphingosine) prevented the SRIF‐14 effect, while phorbol 12‐myristate 13‐acetate enhanced the NMDA response. SRIF‐14 permitted NMDA receptor activation in the presence of 1.2 m M Mg 2+ ions, both in hippocampal synaptosomes and slices. Blockade of inositol‐1,4,5‐trisphosphate (InsP 3 ) receptors with heparin abolished the effect of SRIF‐14. It is concluded that SRIF receptors, possibly of the sst 5 subtype, can exert a permissive role on NMDA receptors colocalized on hippocampal noradrenergic terminals: activation of sst 5 receptors is coupled to pertussis toxin‐sensitive G proteins enhancing phosphoinositide metabolism with activation of InsP 3 receptors and PKC; NMDA receptor subunits might be phosphorylated with consequent removal of the Mg 2+ block in absence of depolarization. British Journal of Pharmacology (2000) 130 , 557–566; doi: 10.1038/sj.bjp.0703346
Год издания: 2000
Авторы: Anna Pittaluga, Andrea Bonfanti, Maurizio Raiteri
Издательство: Wiley
Источник: British Journal of Pharmacology
Ключевые слова: Neuroscience and Neuropharmacology Research, Ion channel regulation and function, Cellular transport and secretion
Другие ссылки: British Journal of Pharmacology (HTML)
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