ANP-(7-23) stimulates a DHP-sensitive Ca2+ conductance and reduces cellular cAMP via a cGMP-independent mechanism.
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/10(6) cells; P less than 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/10(6) cells; P less than 0.01). At 500 nM, ANP-(7-23) also inhibited aldosterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Isales
C M
CM
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Lewicki
J A
JA
Nee
J J
JJ
Barrett
P Q
PQ
D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004553:Electric Conductivity; D007425:Intracellular Membranes / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D015384:Zona Glomerulosa / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
D004095:Dihydropyridines; D010446:Peptide Fragments; D000450:Aldosterone; C038806:1,4-dihydropyridine; D009320:Atrial Natriuretic Factor; C057820:atrial natriuretic factor (7-23); D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium