EVIDENCE FOR ATRIAL-NATRIURETIC-FACTOR INDUCED NATRIURETIC PEPTIDE RECEPTOR SUBTYPE SWITCHING IN RAT PROXIMAL TUBULAR CELLS DURING CULTURE

Culture and natriuretic peptide dependent changes in the expression of the natriuretic peptides atrial natriuretic factor (ANF), brain natri uretic peptide (BNP), and C-type natriuretic peptide (CNP) and the nat riuretic peptide receptors A, B, and C in primary cultures of rat prox imal tubular cells were demonstrated using polymerase chain reaction a nalysis and cyclic guanosine monophosphate response to ANF and CNP. Fr eshly isolated cells expressed mRNA coding for the natriuretic peptide receptor C only, with no expression of the natriuretic peptides or th e natriuretic peptide receptors A or B. At confluence natriuretic pept ide receptor C expression was lost, while mRNA transcripts for both AN F and BNP and the A and B receptors became apparent. The appearance of mRNA transcripts for the natriuretic peptide receptors A and B during cell growth correspond with a significant increase in the cyclic guan osine monophosphate respone to both ANF and CNP, confirming the presen ce of functionally active guanylate cyclase linked A and B natriuretic peptide receptors. The observed changes in peptide receptor expressio n during culture were preceded by changes in natriuretic peptide mRNA expression, suggesting the possibility that natriuretic peptide recept or subtype switching may be under the control of endogenous peptide re lease. Incubation of freshly isolated proximal tubular cells with ANF, BNP, or CNP for 3 h induced similar changes in receptor expression. I ncubation with ANF induced expression of the natriuretic peptide recep tor B and CNP while inhibiting natriuretic peptide receptor C. Incubat ion with BNP induced expression of the natriuretic peptide receptor B and CNP. Incubation with CNP induced expression of the natriuretic pep tide receptors A and B and CNP. These results suggest that primary cul tures of rat proximal tubular cells may experience natriuretic peptide and natriuretic peptide receptor subtype switching as they approach c onfluence under the control of endogenously expressed natriuretic pept ides.