Characterization by affinity cross-linking of a receptor for atrial natriuretic peptide in cultured human thyroid cells associated with reductions in both adenosine 3',5'-monophosphate production and thyroglobulin secretion.
We have previously identified specific atriopeptin (ANP) receptors in cultured human thyroid cells and demonstrated that ANP reduced thyroglobulin (Tg) secretion. In this report the relationship of Tg inhibition to cyclic nucleotide intermediate pathways was explored, and the thyroidal ANP receptor was characterized by affinity cross-linking. Concentrations of Tg, cGMP, and cAMP were measured in medium from thyroid cells cocultured with ANP. ANP significantly inhibited cAMP production at the lower concentration of 0.1 nmol/L and stimulated cGMP levels at a higher concentration of 10 nmol/L. The percentage of inhibition of Tg release over the ANP range of 0.01-10 nmol/L appeared to parallel cAMP, but not cGMP, levels, suggesting that ANP acts via a cAMP pathway in the thyroid. Affinity cross-linking studies characterizing the ANP receptor in thyrocytes and a bovine endothelial cell line known to be cGMP responsive to ANP indicated a single unit ANP receptor of 140 kD coupled to guanylate cyclase in endothelial cells, while a 70-kD receptor was found in thyroid cells which specifically binds to ANP, atriopeptin-I, and atriopeptin-III. These studies in thyrocytes suggest that reduced Tg release may be mediated by a specific single 70-kD ANP receptor associated with an inhibitor cAMP pathway and provide additional insight into the nature of a newly described thyroid-ANP interaction.
Tseng
Y C
YC
Department of Medicine, Walter Reed Army Medical Center, Washington, D.C. 20307-5001.
Lahiri
S
S
Sellitti
D F
DF
Burman
K D
KD
D'Avis
J C
JC
Wartofsky
L
L
D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D006157:Guanosine Monophosphate / Q000378:metabolism; D006801:Humans; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000502:physiology; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism
D011956:Receptors, Cell Surface; D006157:Guanosine Monophosphate; D009320:Atrial Natriuretic Factor; D013954:Thyroglobulin; D000242:Cyclic AMP; D017461:Receptors, Atrial Natriuretic Factor