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pp.103-121
Atrial natriuretic peptide (ANP), a circulating peptide hormone with 28 amino acids secreted from cardiac atria, plays an important role in the maintenance of fluid and electrolytes homeostasis. The actions of ANP appear to be mediated by specific receptors on target cells. However, the specific antagonist for ANP receptors is not yet to be defined. The present study was undertaken to evaluate the antagonistic effects of water extract obtained from the gardenia (Gardenia jasminoides Ellis) on the natriuretic peptide receptor system in the kidney. In the kidney of Sprague Dawley rats, specific 125I-ANP binding sites were localized in glomerulus, inner medulla, intrarenal artery, and vasa recta bundle by using quantitative in vitro receptor autoradiography. These specific bindings were competitively displaced in a dose dependent manner by water extract obtained from the gardenia. Moreover, productions of 3',5'-cyclic guanosine monophosphate (cGMP) via activation of particulate guanylyl cyclase (GC) by ANP were increased in receptor proteins from the glomerulus and inner medulla of rat kidney. These cGMP productions were inhibited in a dose dependent manner by water extract obtained from the gardenia. The inhibitory effect of water extract obtained from the gardenia on activation of GC was quantitatively more potent rather than on 125I-ANP bindings to these renal structures. From affinity cross-linking study on the specific receptor proteins, the water extract obtained from the gardenia inhibited the 125I-ANP labeling of GC-coupled natriuretic peptide receptor from renal glomerulus of rat. Intravenous infusion of ANP elicits the potent diuresis, increment of urine osmolariry, and excretions of urinary chloride, creatinine and PAH in New Zealand White rabbit. These renal effects of ANP were inhibited by the intravenous pre-treatment of water extract obtained from the gardenia without changes in systemic hemodynamics including mean arterial blood pressure and heart rate. These results indicate that the water extract obtained from the gardenia may could be block the GC-coupled natriuretic peptide receptor, and suggest that the extract may contain a natural antagonistic molecule regulating the renal natriuretic peptide system.
