ANP-(7-23) stimulates a DHP-sensitive Ca2+ conductance and reduces cellular cAMP via a cGMP-independent mechanism

C. M. Isales, J. A. Lewicki, J. J. Nee, P. Q. Barrett

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Atrial natriuretic peptide (ANP) potently inhibits aldosterone secretion from the adrenal glomerulosa cell. In many tissues ANP action is associated with an increase in cellular guanosine 3',5'-cyclic monophosphate (cGMP) mediated through binding of the peptide to one of its receptors [ANP-A(R1)]. However, in the adrenal glomerulosa cell, the physiological significance of this rise in cGMP content has been contested. In an effort to determine whether non-cyclase-containing ANP receptors, such as ANP-C(R2), are linked to any of the events triggered by ANP binding, we utilized a truncated ANP analogue, ANP-(7-23), which at low doses exhibits selectivity for the ANP- C(R2) receptor. With the use of bovine adrenal glomerulosa cells, low concentrations (1 nM) of ANP-(7-23) failed to stimulate cGMP production, did not lower cytosolic calcium in the presence of low K+, and did not inhibit aldosterone secretion. At 1 nM, however, the analogue decreased cellular adenosine 3',5'-cyclic monophosphate content [8.27 ± 0.51 vs. 6.74 ± 0.09 (SE) pmol/106 cells; P < 0.02] and, only in the presence of high extracellular [K+], increased cytosolic calcium. This ANP-induced rise in cytosolic calcium was abolished by the addition of a low dose (30 nM) of the dihydropyridine nitrendipine. ANP-(7-23) when utilized at a higher concentration (500 nM) lost its selectivity for the ANP-R2 receptor and increased cellular cGMP content (control, 0.27 ± 0.02 vs. 500 nM ANP-(7-23), 0.448 ± 0.02 pmol/106 cells; P < 0.01). At 500 nM, ANP-(7-23) also inhibited aldosterone secretion. Taken together, these data suggest that a noncyclase-containing receptor, possibly the ANP-C(R2) receptor, transduces a calcium signal which may play a role in mediating the agonist actions of ANP observed in other tissues.

Original languageEnglish (US)
Pages (from-to)C334-C342
JournalAmerican Journal of Physiology - Cell Physiology
Volume263
Issue number2 32-2
DOIs
StatePublished - Jan 1 1992
Externally publishedYes

Keywords

  • adrenal
  • aldosterone
  • cyclic nucleotides
  • cytosolic calcium
  • glomerulosa cells

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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