[Recent knowledge about the metabolic regulation of coronary circulation, with a contribution on adenine nucleotide metabolism of coronary endothelial cells].
The adenosine hypothesis in its original form neglects other myocardial tissues besides the predominant cardiomyocyte compartment. We could, however, demonstrate that the coronary endothelium comprises a metabolically very active adenosine and adenine nucleotide compartment of the heart, and functions as an impermeable metabolic barrier for interstitially or intravascularly accumulating adenosine if the vasoactive nucleoside is present at concentrations less than 10(-6) M. As a consequence, the vasodilatory action of intracoronarily applied adenosine cannot result from a direct action on the smooth muscle cells of the arterioles, but must be mediated by the endothelium. Since high molecular weight derivatives of adenosine, which are clearly confined to the coronary system, can also induce a very prompt coronary flow increase when applied intravascularly, smooth muscle relaxation must be triggered by an extracellular adenosine receptor at the luminal surface of the endothelium. According to preliminary pharmacological studies, this receptor belongs to the A2-type and thus stimulates the endothelial adenylate cyclase system. On the basis of our findings it is evident that with respect to the vasodilating effect of adenosine one has to distinguish between its action from the interstitial space directly via the putative receptor at the surface of the arteriolar smooth muscle cells, and its action from the intravascular space via the newly detected endothelial A2-receptor. It is a matter of further experimentation to determine to what extent both receptor populations actually participate in the metabolic regulation of coronary flow under physiological and pathophysiological conditions.
D000227:Adenine Nucleotides / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000201:enzymology*; D004727:Endothelium / Q000201:enzymology; D006801:Humans; D009206:Myocardium / Q000201:enzymology; D011956:Receptors, Cell Surface / Q000378:metabolism; D011983:Receptors, Purinergic; D014664:Vasodilation
D000227:Adenine Nucleotides; D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D000262:Adenylyl Cyclases; D000241:Adenosine
Neuere Erkenntnisse über die metabolische Koronarflussregulation, zugleich ein Beitrag zum Adeninnukleotidstoffwechsel koronarer Endothelzellen.