Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The alpha 1-adrenergic receptor exists as at least two distinct subtypes, alpha 1a and alpha 1b. Based on hydrophobic exclusion studies and limited proteolysis of the cloned receptor, it appears to possess characteristics analogous to other membrane-bound receptors including seven membrane spanning domains, three extracellular, and three intracellular loops, with extensive glycosylation near the extracellular amino terminus. Although the receptor is coupled to phospholipase C in cardiac myocytes, with activation resulting in the production of inositol trisphosphate (IP3) and diacylglycerol, recent findings suggest that the receptor may also be linked to phospholipase A2, phospholipase D, and cyclic nucleotide phosphodiesterase. The alpha 1-adrenergic receptor has been shown to increase in response to myocardial ischemia in a number of different species and to mediate not only positive inotropic effects, but also to contribute substantially to arrhythmogenesis. The increase in alpha 1-adrenergic receptors can also occur in isolated adult ventricular myocytes in response to hypoxia, a mechanism which appears to be secondary to the sarcolemmal accumulation of long-chain acylcarnitines. This increase in alpha 1-adrenergic receptors in hypoxic myocytes is also linked to an enhanced increase in IP3 in response to receptor stimulation. These and other findings obtained in vivo during ischemia suggest that alpha 1-adrenergic mechanisms can become prominent in myocardium under pathophysiologic conditions in which a depressed contractile state exists and may therefore serve as a secondary inotropic system. However, the arrhythmogenic effects of stimulation of the alpha 1-adrenergic receptor in the ischemic heart in man may contribute substantially to arrhythmogenesis and, thereby, to the incidence of sudden cardiac death.
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PMID:Modulation of alpha-adrenergic receptors and their intracellular coupling in the ischemic heart. 196 2

Adenosine released during cardiac ischemia exerts a marked protective effect in the heart that is mediated by the A(1) and A(3) subtypes of adenosine receptors. The signaling pathways activated by these adenosine receptors have now been characterized in a chick embryo ventricular myocyte culture model of cardioprotection against ischemia. Selective A(1) and A(3) receptor agonists were shown to activate phospholipases C and D, respectively, to achieve their distinct cardioprotective effects. The specificity of the A(3) receptor-phospholipase D interaction was also demonstrated in chick embryo atrial myocytes (which do not express endogenous A(3) receptors) that had been transfected with a vector encoding the human A(3) receptor. Activation of both endogenous A(1) and A(3) receptors in ventricular myocytes resulted in a protective response greater than that induced by stimulation of either receptor alone. Agonists that activate both adenosine A(1) and A(3) receptors may thus prove beneficial for the treatment of myocardial ischemia.
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PMID:Distinct cardioprotective effects of adenosine mediated by differential coupling of receptor subtypes to phospholipases C and D. 1087 35