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Regulatory peptides v.44 no.2, 1993년, pp.149 - 157  

Signal transduction mediated by angiotensin II receptor subtypes expressed in rat renal mesangial cells

Madhun, Z.T. ; Ernsberger, P. ; Ke, F.-C. ; Zhou, J. ; Hopfer, U. ; Douglas, J.G. ;
  • 초록  

    Recent evidence suggests that there are two classes of receptors for angiotensin II (AngII), AT 1 which is sensitive to losartan (DuP753) and is G-protein coupled, and AT 2 which is sensitive to both PD123319 and CGP42112A, and is non-G-protein coupled. In rat mesangial cells two subtypes of AT 1 receptor could be distinguished, AT 1A subtype is more sensitive to losartan whereas AT 1B subtype is more sensitive to PD123319, but insensitive to CGP42112A. The present studies were designed to ascertain which receptor subtype mediates three AngII-induced physiologic functions in rat mesangial cells namely intracellular Ca 2+ mobilization, adenylyl cyclase inhibition and protein synthesis as monitored via [ 3 H]leucine incorporation. The rank order of potency for inhibition of AngII-induced [Ca 2+ ] i mobilization and adenylyl cyclase regulation was PD123319≤losartan>CGP42112A. By contract, lasartan was quite effective at inhibiting protein synthesis (IC 50 =8 8 nM) while PD123319 was without effect. These findings are consistent with AngII mediated signal transduction through AT 1A and AT 1B sites for phospholipase C mediated [Ca 2+ ] i mobilization and inhibition of adenylyl cyclase. On the other hand, AT 1A receptors appear to exclusively mediate AngII-induced protein synthesis. These observations underscore the complexity of AngII mediated signal transduction in glomerular mesangium.


  • 주제어

    Angiotensin II antagonist .   Rat mesangial cell .   Phospholipase C .   Calcium ion mobilization .   Adenylyl cyclase .   Protein synthesis.  

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