Effect of zelandopam, a dopamine D1-like receptor agonist, in puromycin aminonucleoside nephrosis rats.
The present experiment was designed to investigate the role of peripheral dopamine D1-like receptors and to evaluate the prophylactic effect of zelandopam, a dopamine D1-like receptor agonist, on puromycin aminonucleoside (PA)-induced nephrosis in rats. Rats were divided into six groups (n=10 per group): 0.9% saline-injected rats (control); PA-injected rats (PAN); PA-injected rats treated with the selective dopamine D1-like receptor agonist zelandopam (30, 100, 300 mg/kg p.o. twice a day); PA-injected rats treated with prednisolone (1 mg/kg p.o. once a day). Nephrosis was induced in rats with a single intravenous injection of PA at a dose of 50 mg/kg. The effects of zelandopam and prednisolone in PA nephrosis rats were evaluated before injection of PA and at 7 and 14 days after injection. PA-induced nephrosis was characterized by an increase in urinary protein excretion (proteinuria) and plasma total cholesterol. Zelandopam dose-dependently attenuated the increase in proteinuria and total cholesterol. Prednisolone significantly attenuated the increase in proteinuria and total cholesterol and resulted in a significant decrease in body weight. The present study demonstrates for the first time that zelandopam, a selective dopamine D1-like receptor agonist, is effective in blunting the development of PA-induced nephrosis, and that the effects of zelandopam are dose dependent.
Yatsu
Takeyuki
T
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. yatsu@yamanouchi.co.jp
Aoki
Motonori
M
Tanaka
Akihiro
A
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D009401:Nephrosis / Q000139:chemically induced / Q000517:prevention & control*; D011239:Prednisolone / Q000494:pharmacology; D011507:Proteinuria / Q000517:prevention & control; D011692:Puromycin Aminonucleoside; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000502:physiology; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D013997:Time Factors
D017447:Receptors, Dopamine D1; D044005:Tetrahydroisoquinolines; D011692:Puromycin Aminonucleoside; D011239:Prednisolone; C073504:zelandopam