• The Korean Journal of Physiology and Pharmacology
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• 제1권3호
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• pp.325-335
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• 1997

Evidence for the existance of at least two subclasses of renal adenosine receptors has been presented. N-6-cyclohexyladenosine (CHA) is a relatively selective $A_1$ adenosine agonists, whereas 5'-N-ethylcarboxamidoadenosine (NECA) acts as a preferential agonist of $A_2$ adenoisne receptor. N6-(L-2-phenylisoproryl)-adenosine (PIA) almost unselectively activates both $A_1\;and\;A_2$ 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-phenyl-xanthine (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.

• 대한약리학회지
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• 제22권2호
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• pp.79-87
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• 1986

중추 dopamine(DA)계가 신장기능 조절에 관여하고 있으며 뇌실내로 DA를 투여하면 norepinephrine(NE)처럼 항이뇨와 항Na 배설을 초래함이 보고된 바 있고, 중추 DA작용에 있어서 adrenergic system이 관여한다는 많은 시사가 있다. 따라서 본 연구에서는alpha-2 adrenocopter 차단제인 yohimbine이 측뇌실내 DA의 신장작용에 어떠한 영향을 미치는가를 관찰하였다. Yohimbine $100\;{\mu}g/kg$을 가토측뇌실내로 투여시(icv) 신혈류 및 사구체 여과율의 감소와 함께 현저한 항이뇨 및 Na 배설감소를 초래하였으며, DA $15\;{\mu}g/kg$ icv 역시 항이뇨를 초래하였으나 yohimbine 전 처치후에는 뇨량 및 Na배설의 증가를 초래하였다. 양을 더올려 $150\;{\mu}g/kg$의 DA를 yohimbine 전처치 가토에 투여하면 3배 이상의 Na배설 증가와 함께 현저한 이뇨작용이 나타났으며 이 작용은 약 20분간 지속되었다. 이때 신혈류 역학은 일부 개선되었다. 다른 DA agonist인 apomorphine은 $100\;{\mu}g/kg$ icv로 현저한 이뇨와 Na 배설증가를 나타내며 신혈류역학도 개선하였으나, yohimbine은 이같은 apomoiphine작용을 차단하지 못하였다. NE $10\;{\mu}g/kg$ icv도 항이뇨 작용을 나타냈으나 yohimbine 전처치에 의하여 차단되지 아니하였다. 이 연구결과로, 중추 DA의 신장작용은 NE처럼 단순하지 않고, 이뇨작용은 신혈류역학의 감퇴에 기인한 항이노작용에 의해 은폐되어 있으며, yohimbine은 DA의 항이뇨작용은 차단하나 이뇨작용에는 영향을 미치지 못하며, DA의 항이뇨작용이 지양될때에만 이뇨작용이 발현됨을 알 수 있었다. 또한 중추를 통한 DA의 신장작용에는 adrenergic system이 관여하지 않은 것으로 보인다.

• Biomolecules & Therapeutics
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• 제1권2호
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• pp.211-219
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• 1993

The general and some pharmacological actions of DWP 302 were investigated in animals and the following results were obtained. In central nervous system, DWP 302 had no effects on the pentobarbital induced anaesthesia, locomotor activity, rotarod test, traction test, analgesic action in the mice and body temperature in the rat. DWP 302 showed no depressive action on the convulsion induced by strychnine and electronic shock. From these results, DWP 302 was considered to have no or little pharmacological effect on the central nervous system. Furthermore, DWP 302 had no influences on the normal blood pressure and heart rate. In the isolated ileum of guinea pig, DWP 302 showed neither contractive nor relaxing effects against the acetylcholine ($10^{-6}g/mι$), histamine ($10^{-6}g/mι$) and $BaCl_2$ ($10^{-4}g/mι$) at a concentration of $1.9{\times}10^{-4}g/mι$ in bath. But it caused a slight increase in basal tone at a concentration of $6.3{\times}10^{-4}g/mι$ and this effect was inhibited by atropine $10^{-7}g/mι.$ In the isolated trachea and vas deference, DWP 302 showed no effect on the contractions produced by histamine and norepinephrine, respectively. And DWP 302 showed no effect on the contractions produced by acetylcholine and oxytocin in the isolated nonpregnant rat uterus. DWP 302 had no effect on bile excretion, urine volume, pH and gastrointestinal motility, But, DWP 302 showed a significant inhibitory effect on gastric secretion in the rat.

• Journal of Yeungnam Medical Science
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• 제34권2호
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• pp.247-253
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• 2017

Approximately 10-15% of pheochromocytomas are malignant. There are insufficient histologic criteria for the diagnosis of malignant pheochromocytoma. Thus, the term malignant pheochromocytoma is restricted to tumors with local invasion or distant metastases. We experienced a case of malignant pheochromocytoma recurred with spinal metastasis 4 years after the surgery for huge benign pheochromocytoma. A 68-year-old female was admitted for trunk and back pain. The patient had a history of surgery 4 years ago for a $10.0{\times}9.5{\times}7.5cm$ sized benign pheochromocytoma at the left adrenal gland. A thoracolumbar magnetic resonance imaging showed a tumor in the 7th thoracic vertebral body and a 24-hour urinary norepinephrine increased, suggesting metastatic recurrence of malignant pheochromocytoma. After metastasectomy in the 7th thoracic vertebral body, urine catecholamine was normalized and pain also disappeared. However, a metastatic lesion was found in the paraaortic area on a follow-up abdominal computed tomography scan and an additional metastasectomy was performed. The pathology confirmed the diagnosis of metastatic pheochromocytoma in the paraaortic lymph nodes. She is supposed to be treated with adjuvant iodine 131-meta-iodobenzylguanidine therapy. In our experience, a close follow-up should be considered in patients who had a huge benign pheochromocytoma due to the possibility of malignant metastases.