Differential expression of adenylyl cyclase subtypes in human cardiovascular system.
In human myocardium, beta1-adrenoceptor stimulation achieves maximal inotropic response but less than 50% of maximal adenylyl cyclase activation, whereas the reverse is true of the beta2-adrenoceptor. Four types of adenylyl cyclase, type IV-VII, have been described in mammalian heart, but their expression and relative distribution in human heart and blood vessels is not known. We found that type IV, V, VI and VII adenylyl cyclases were all expressed in cardiomyocytes. Whereas types IV and VII RNA were more abundant in extra-cardiac than cardiac tissues, both absolute and relative expression of type VI was greatest in heart, and lower in tissues lacking a beta1-adrenoceptor. Type V expression was virtually confined to atrium. In situ mRNA hybridisation showed that the beta1-adrenoceptor co-localised with type VI adenylyl cyclase but not other subtypes in juxtoglomerular cells of human kidney. The tissue specific expression of these adenylyl cyclase subtypes may favour its coupling to corresponding receptors expressed in the given tissue type.
Clinical Pharmacology Unit, Addenbrooke's Centre for Clinical Investigation (ACCI), Box 110, Addenbrooke's Hospital, Hills Road, University of Cambridge, Cambridge CB2 2QQ, UK. tao.wang@man.ac.uk
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Brown
D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism; D002319:Cardiovascular System / Q000737:chemistry / Q000201:enzymology*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006325:Heart Atria / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007606:Juxtaglomerular Apparatus / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism
D007527:Isoenzymes; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D000262:Adenylyl Cyclases