Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An experimental procedure has been designed to permit the simultaneous assessment of the activation status of the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) with insulin secretion in perifused islets. By this procedure, the activation of CaM kinase II by glucose correlated closely with the initial and sustained phases of insulin secretion within a 30-min test period. By contrast, islets (160-200/tube) in static incubations neither supported second-phase insulin secretion nor CaM kinase II activation beyond 10-15 min. This was not the result of the accumulation of insulin, because the introduction of insulin (40-160 ng/ml) into the perifusion medium failed to mimic the suppression of glucose-induced insulin secretion or CaM kinase II activation. A similar addition of SRIF (0.01-1 microM) or epinephrine (1 microM) profoundly suppressed insulin secretion although failing to significantly influence CaM kinase II activation. Finally, on withdrawal of glucose from perifused islets, insulin secretion rapidly returned to basal rates, but CaM kinase II deactivation was significantly delayed. The correlation of kinase activation with the initiation of insulin secretion suggests that CaM kinase II may be important in the regulation of glucose-induced insulin secretion. The observed dissociation of these parameters in the presence of inhibitory hormones or after the withdrawal of a glucose stimulus, however, suggests that the kinase is not directly involved in the final steps of insulin exocytosis.
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PMID:Correlation of the activation of Ca2+/calmodulin-dependent protein kinase II with the initiation of insulin secretion from perifused pancreatic islets. 916 23

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 Mg2+-free solutions. Here, we first confirm the pharmacology of these receptors using selective sst5 ligands in Mg2+-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]-1H-indol-3-yl]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione] and by the nonreceptor tyrosine kinase (Src) inhibitors PP2 [3-(4-chlorophenyl)1-(1,1-dimethylethyl)-1H-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-[([17beta]-3-methoxyextra-1,3,5[10]-trien-17-yl)amino]hexyl)-1H-pyrrole-2,5-dione] and by the Ca2+/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 Mg2+-free medium but failed to permit NMDA receptor activation in presence of external Mg2+ ions. The results suggest the involvement of CaMKII in the sst5 receptor-mediated activation of NMDA receptors in presence of Mg2+ and of the PLC/PKC/Src pathway in the up-regulation of the ongoing NMDA receptor activity.
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PMID: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. 1560 72

Excessive activation of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with numerous diseases, including depression, and the tricyclic antidepressant imipramine has been shown to suppress activity of the HPA axis. Central hypothalamic control of the HPA axis is complex and involves a number of neuropeptides released from multiple hypothalamic subnuclei. The present study was therefore designed to determine the effects of imipramine administration on the mouse hypothalamus using a peptidomics approach. Among the factors found to be downregulated after acute (one day) or chronic (21 days) imipramine administration were peptides derived from secretogranin 1 (chromogranin B) as well as peptides derived from cerebellin precursors. In contrast, peptides SRIF-14 and SRIF-28 (1-11) derived from somatostatin (SRIF, somatotropin release inhibiting factor) were significantly upregulated by imipramine in the hypothalamus. Because diminished SRIF levels have long been known to occur in depression, a second part of the study investigated the roles of individual SRIF receptors in mediating potential antidepressant effects. SRA880, an antagonist of the somatostatin-1 autoreceptor (sst1) which positively modulates release of endogenous SRIF, was found to synergize with imipramine in causing antidepressant-like effects in the tail suspension test. Furthermore, chronic co-administration of SRA880 and imipramine synergistically increased BDNF mRNA expression in the cerebral cortex. Application of SRIF or L054264, an sst2 receptor agonist, but not L803807, an sst4 receptor agonist, increased phosphorylation of CaMKII and GluR1 in cerebrocortical slices. Our present experiments thus provide evidence for antidepressant-induced upregulation of SRIF in the brain, and strengthen the notion that augmented SRIF expression and signaling may counter depressive-like symptoms. This article is part of a Special Issue entitled 'Anxiety and Depression'.
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PMID:Neuropeptidomics of mouse hypothalamus after imipramine treatment reveal somatostatin as a potential mediator of antidepressant effects. 2185 15