The dynamics of the guanylate cyclase receptor of atrial natriuretic factor (GC(A)-ANF receptor) were investigated in cultured glomerular mesangial and renomedullary interstitial cells from the rat. In these cells, the GC(A)-ANF receptor did not mediate internalization and lysosomal hydrolysis of 125I-ANF1-28 and did not undergo ligand-induced endocytosis. Glomerular mesangial cells were able, however, to mediate internalization and lysosomal hydrolysis of 125I-ANF1-28 via clearance ANF (C-ANF) receptors and to promote rapid receptor-mediated internalization and lysosomal hydrolysis of 125I-(Sar1) angiotensin II. Radioligand specifically bound to surface GC(A)-ANF receptors was rapidly dissociated at 37 °C (k(off) > 0.8 min-1), with a Q10 (30-37 °C) > 6. The dissociation was markedly slower at subphysiological temperatures (Q10(4-30 °C), 2-3) or in the presence of 0.5 mM amiloride. The results demonstrate that the GC(A)-ANF receptor, contrary to C-ANF receptors and most other polypeptide hormone receptors, is a membrane resident protein that does not mediate internalization and lysosomal hydrolysis of ligand. The termination of the interaction of ANF with GC(A)-ANF receptors results from a physiological process that leads to rapid dissociation of receptor-ligand complexes. The unique dynamics of GC(A)-ANF receptor-ligand complexes are likely to contribute importantly to stimulus-response homeostasis of ANF.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Biological Chemistry|
|State||Published - Jan 1 1992|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology