Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate further the inhibition of platelet aggregation by a plasma factor(s) in unipolar depression, a series of assays were performed in which the platelet-rich plasma of a male volunteer was preincubated with the plasma of either unmedicated unipolar depressed patients or age-matched controls. Platelet aggregation was initiated by the following aggregating agents; ADP (10 and 2.5 microM), ADP/5HT (0.5 microM ADP + 50 microM 5HT and 0.5 microM ADP + 25 microM 5HT) and adrenaline (10 and 1 microM) (that act on different platelet membrane receptors) and by the following agents; sodium fluoride (20 mM), calcium ionophore A23,187 (19 microM) and phorbol-12-myristate-13-acetate (3.24 microM) (that act at specific intracellular sites). The plasma of depressed patients significantly reduced the platelet aggregatory response for each of the aggregating agents at each of the concentrations tested. Therefore, it is concluded that the inhibition of platelet aggregation by a plasma factor(s) may be irreversible in nature and may have an intracellular site(s) of action, possibly at, or beyond, the site of activated protein kinase C.
 ...
PMID:Further characterization of the inhibition of platelet aggregation by a plasma factor(s) in unmedicated unipolar depressed patients. 779 Jun 76

Over the past decade, the focus of research into the pathophysiology of mood disorders (bipolar disorder and unipolar depression in particular) has shifted from an interest in the biogenic amines to an emphasis on second messenger systems within cells. Second messenger systems rely on cell membrane receptors to relay information from the extracellular environment to the interior of the cell. Within the cell, this information is processed and altered, eventually to the point where gene and protein expression patterns are changed. There is a preponderance of evidence implicating second messenger systems and their primary contact with the extracellular environment, G proteins, in the pathophysiology of mood disorders. After an introduction to G proteins and second messenger pathways, this review focuses on the evidence implicating G proteins and two second messenger systems-the adenylate cyclase (cyclic adenosine monophosphate, cAMP) and phosphoinositide (protein kinase C, PKC) intracellular signaling cascades-in the pathophysiology and treatment of bipolar disorder and unipolar depression. Emerging evidence implicates changes in cellular resiliency, neuroplasticity and additional cellular pathways in the pathophysiology of mood disorders. The systems discussed within this review have been implicated in neuroplastic processes and in modulation of many other cellular pathways, making them likely candidates for mediators of these findings.
 ...
PMID:Signaling networks in the pathophysiology and treatment of mood disorders. 1216 43

Monoaminergic-based drugs remain the primary focus of pharmaceutical industry drug discovery efforts for mood disorders, despite serious limitations regarding their ability to achieve remission. The quest for novel therapies for unipolar depression and bipolar disorder has generally centered on two complementary approaches: (1) understanding the presumed therapeutically relevant biochemical targets of currently available medications, and using that knowledge to design new drugs directed at both direct biochemical targets and downstream targets that are regulated by chronic drug administration; and (2) developing pathophysiological models of the illness to design therapeutics to attenuate or prevent those pathological processes. This review describes several promising drugs and drug targets for mood disorders using one or both of these approaches. Agents interacting with non-catecholamine neurotransmitter systems with particular promise for unipolar and bipolar depression include excitatory amino acid neurotransmitter modulators (eg, riluzole, N-methyl-D-aspartate antagonists, and AMPA receptor potentiators) and neuropeptide antagonists (targeting corticotropin releasing factor-1 and neurokinin receptors). Potential antidepressant and mood-stabilizing agents targeting common intracellular pathways of known monoaminergic agents and lithium/mood stabilizers are also reviewed, such as neurotrophic factors, extracellular receptor-coupled kinase (ERK) mitogen-activated protein (MAP) kinase and the bcl-2 family of proteins, and inhibitors of phosphodiesterase, glycogen synthase kinase-3, and protein kinase C. A major thrust of drug discovery in mood disorders will continue efforts to identify agents with rapid and sustained onsets of action (such as intravenous administration of ketamine), as well as identify drugs used routinely in non-psychiatric diseases for their antidepressant and mood-stabilizing properties.
 ...
PMID:Novel drugs and therapeutic targets for severe mood disorders. 1817 33