Adenosine 수용체 작동제 장기 투여의 신장효과

• 영문명: Renal Effects of Chronic Treatment of Adenosine Analogues
• 발행기관: 대한생리학회-대한약리학회
• 저자명: 김택희(Tack Hee Kim) 김선희(Suhn Hee Kim) 허종(Jong Huh) 조경우(Kyung Woo Cho)
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제1권 제3호, 325~335쪽, 전체 11쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 1997.01.01

영문 초록

Evidence for the existance of at least two subclasses of renal adenosine receptors has been presented. N-6- cyclohexyladenosine (CHA) is a relatively selective A₁ adenosine agonists, whereas 5 -N-ethylcarboxamidoadenosine (NECA) acts as a preferential agonist of A₂ adenoisne receptor. N6-(L-2-phenylisopropyl)-adenosine (PIA) almost unselectively activates both A₁ and A₂ adenosine receptors at micromolar concentrations. During the characterization of adenosine receptor in the kidney, we have discovered a novel phenomenon, that is, an intramuscular administration of CHA for 3 days caused a diuresis and a suppression of urinary concentrating ability. To further characterize this novel phenomenon, an intramuscular administration of adenosine and other adenosine angonists, PIA and NECA, and prior treatment of adenosine antagonists, caffeine, theophylline and 1,3-diethyl-8-phenylxanthine (DPX) were performed.

Systemic administration of CHA, PIA, and NECA for 3 days caused a suppression in heart rate, blood pressure and general motor activity without change in rectal temperature.

Systemic administration of CHA, 0.5, 1 and 2 mg/kg/day, for 3 days caused a dose-dependent increase in urine volume and decrease in urinary osmolarity and free water reabsorption. This phenomenon was reversible and repeatable. Administration of adenosine (40 mg/kg/day) produced no apparent effect on the renal function, whereas PIA (2 mg/kg/day) produced an similar effect to CHA on the renal function.

Systemic adminstration of NECA, 0.025, 0.05 and 0.25 mg/kg/day, for 3 days caused a dose-dependent increase in urine volume and dose-dependent increases in excreted amount of creatinine, urinary osmolarity and free water reabsorption. These renal effects of adenosine agonist were maximum at second day during the drug administration. In terms of increase in urine volume and the suppression of urinary concentrating ability, NECA was potent than CHA.

Prior treatment of caffeine (50 mg/kg/day) or theophylline (50 mg/kg/day) abolished the diuretic effect of CHA, whereas DPX (50 mg/kg/day) did not affect the CHA effect. CHA, 0.5 mg/kg/day, produced no change in plasma renin activity and plasma levels of aldosterone, epinephrine, and norepinephrine.

These results suggest that this novel phenomenon produced by an activation of renal adenosine receptors plays an important role in urinary concentrating mechanism.

키워드

Adenosine Kidney Agonist Antagonist Renin Catecholamine Aldosterone Blood pressure Heart rate Temperature