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Distribution and regulation of natriuretic factor-R1C receptor subtypes in mammalian cell lines

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Abstract

The differential distribution of natriuretic peptide receptor subtypes and their distinct properties were assessed in mammalian cellular models which were screened for their ability to produce cGMP upon stimulation by different natriuretic peptides. The ANF-R1A receptor subtype was distinguished by its selective activation by atrial natriuretic factor (ANF) while the ANF-R1C was characterized by preferential stimulation by C-type natriuretic peptide (CNP). AT-t20 pituitary cells, bovine adrenal chromaffin cells, and NIH-3T3 fibroblasts mainly express the ANF-R1C receptor subtype. Other cell lines such as PC12, RASM and GH3 express significant but varying amounts of both ANF-R1A and ANF-R1C subtypes. A10 and NIH cells which express high density of ANF-R2 receptor subtype, also demonstrate a higher sensitivity to CNP over ANF suggesting that they express significant amounts of ANF-R1C. Studies of the regulation by ATP of guanylyl cyclase activity indicate that both ANF-R1A and ANF-R1C subtypes are modulated in the same manner. In the presence of Mn2+, ATP inhibits the CNP-stimulated guanylyl cyclase activity while in the presence of Mg2+ adenine nucleotides potentiate the stimulation by CNP. In addition, we show that like the ANF-R1A, the ANF-R1C guanylyl cyclase activity can be regulated by phosphorylation since preincubation with TPA or FKL attenuates the subsequent stimulation by CNP in cultured cells. The results presented demonstrate that specific cell types express distinct natriuretic peptide receptor subtypes and also that the newly characterized ANF-R1C subtype is regulated by ATP and serine/threonine kinases in the same way as the ANF-R1A subtype.

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Abbreviations

ANF:

atrial natriuretic factor

BNP:

brain natriuretic peptide

CNP:

C-type natriuretic peptide

ATP:

adenosine-5′-triphosphate

IBMX:

3-isobutyl-1-methylxanthine

TPA:

12-O-tetradecanoyl-phorbol-13-acetate

FKL:

forskolin

PKC:

calcium-phospholipid-dependent protein kinase

PKA:

cAMP-dependent protein kinase

PKG:

cGMP-dependent protein kinase

C-ANF:

[Cys116]-ANF-(102-116)-NH2

CC:

chromaffin cells

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, University of Montreal, Succursale A, C.P.6128, H3C 3J7, Montréal, Canada

    J. Féthière (Recipient of a studentship), H. Ong & A. De Léan

  2. Heart and Stroke Foundation of Canada, Canada

    J. Féthière (Recipient of a studentship)

  3. Faculty of Pharmacy, University of Montreal, Montréal, Canada

    K. Babinski & H. Ong

  4. Medical Research Council of Canada, Canada

    L. Larose (Recipient of a Fellowship) & K. Babinski

Authors
  1. J. Féthière
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  2. R. Graihle
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  3. L. Larose
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  4. K. Babinski
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  5. H. Ong
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  6. A. De Léan
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Féthière, J., Graihle, R., Larose, L. et al. Distribution and regulation of natriuretic factor-R1C receptor subtypes in mammalian cell lines. Mol Cell Biochem 124, 11–16 (1993). https://doi.org/10.1007/BF01096376

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  • DOI: https://doi.org/10.1007/BF01096376

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