TY - JOUR
T1 - ANP-(7-23) stimulates a DHP-sensitive Ca2+ conductance and reduces cellular cAMP via a cGMP-independent mechanism
AU - Isales, C. M.
AU - Lewicki, J. A.
AU - Nee, J. J.
AU - Barrett, P. Q.
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
KW - adrenal
KW - aldosterone
KW - cyclic nucleotides
KW - cytosolic calcium
KW - glomerulosa cells
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U2 - 10.1152/ajpcell.1992.263.2.c334
DO - 10.1152/ajpcell.1992.263.2.c334
M3 - Article
C2 - 1325113
AN - SCOPUS:0026670028
SN - 0002-9513
VL - 263
SP - C334-C342
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 2 32-2
ER -