Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.6.1.1 (
adenylate cyclase
)
19,190
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Guanine nucleotide-binding regulatory proteins (G proteins) play a major role in the regulation of a number of physiological processes, such as stimulation or Inhibition of
adenylate cyclase
activity or gaiting of ionic channels. Myocardial ischemia could induce the changes in receptor-G protein signal transduction system in the heart. Therefore, this article will focus on the role and alterations of G proteins (especially, Gs and Gi) in myocardial ischemia. The Gi protein rapidly loses functional activity during very early myocardial ischemia. In contrast to Gi protein, the function of Gs protein during this phase has not been evaluated. Moreover, the changes in Gs protein after 30 min of ischemia are contradictory. However, the sensitization of the
adenylate cyclase
activity in the very early phase of acute ischemia is gradually replaced by a decrease in
adenylate cyclase
activity with prolonged ischemia. The decrease in the function and amount of Gs protein may be one of the factors that induce these changes. The function of Gs protein was also decreased in the canine hearts with ischemia and reperfusion. In contrast to ischemia and reperfusion, there are no significant alterations in G proteins and modulation of
adenylate cyclase
in the stunned myocardium. It has become increasingly evident that Gi protein may play an important role in the cardioprotective effects of preconditioning. When beta-adrenoreceptor densities are reduced in
chronic myocardial ischemia
, decreased in the amount and function of Gi protein and increased amount of Gs protein may play the role in preservation of the
adenylate cyclase
activity. These alterations in G proteins may play the important role in the myocardial function during myocardial ischemia.
...
PMID:The guanine nucleotide-binding regulatory proteins (G proteins) in myocardium with ischemia. 890 69
Altered platelet physiology may contribute to the emergence of thrombosis in patients with many forms of cardiovascular disease. Excess platelet activation may reflect increased stimulation of pro-aggregatory pathways. There is, however, increasing evidence that excessive platelet response, due to impaired efficacy of anti-aggregatory autacoids such as nitric oxide (NO) and prostacyclin (PGI
2
), may be just as important. For example, diminished platelet response to NO has been documented in acute and
chronic myocardial ischaemia
, heart failure, aortic valve disease and in the presence of hyperglycaemia. This "NO resistance" has been shown to reflect both the scavenging of NO by reactive oxygen species and dysfunction of its intracellular "receptor", soluble guanylate cyclase. Importantly, these abnormalities of NO signalling are potentially reversible through judicious application of pharmacotherapy. The analogous condition of impaired PGI
2
/
adenylate cyclase
(AC) signalling has received comparatively less attention to date. We have shown that platelet response to prostaglandin E
1
(PGE
1
) is frequently impaired in patients with symptomatic myocardial ischaemia. Because the effects of ADP receptor antagonists such as clopidogrel and ticagrelor at the level of the P2Y
12
receptor are coupled with changes in activity of AC, impaired response to PGE
1
might imply both increased thrombotic risk and a reduced efficacy of anti-aggregatory drugs. Accordingly, patient response to treatment with clopidogrel is determined not only by variability of clopidogrel bio-activation, but also extensively by the integrity of platelet AC signalling. We here review these recent developments and their emerging therapeutic implications for thrombotic disorders.
...
PMID:New Developments in Platelet Cyclic Nucleotide Signalling: Therapeutic Implications. 2735 71
