• The Korean Journal of Physiology
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• v.23 no.2
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• pp.363-375
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• 1989

It has been well known that peripheral infusion of angiotensin II results in an increase of blood pressure, and an elevation of aldosterone secretion, and an inhibition of renin relase. However, the direct effect of angiotensin II on renal function has not been clearly established. In the present study, to investigate the effect of angiotensin II on renal function and renin release, angiotensin II (0.3, 3 and 10 ng/kg/min) was infused into a unilateral renal artery of the unanesthetized rabbit and changes in renal function and active and inactive renin secretion rate (ARSR, IRSR) were measured. In addition, to determine the relationship between the renal effect of angiotensin II and adenosine, the angiotensin II effect was evaluated in the presence of simultaneously infused 8-phenyltheophylline (8-PT, 30 nmole/min), adenosine A 1 receptor antagonist. Angiotensin II infusion at dose less than 10 ng/kg/min decreased urine flow, clearances of para-amino-hippuric acid and creatinine, and urinary excretion of electrolytes in dose-dependent manner. The changes in urine flow and sodium excretion were significantly correlated with the change in renal hemodynamics. Infusion of angiotensin II at 10 ng/kg/min also decreased ARSR, but it has no significant effect on IRSR. The change in ARSR was inversely correlated with the change in IRSR. The plasma concentration of catecholamine was not altered by an intarenal infusion of angiotensin II. In the presence of 8-PT in the infusate, the effect of angiotensin II on renal function was significantly attenuated, but that on renin secretion was not modified. These results suggest that the reduction in urine flow and Na excretion during intrarenal infusion of angiotensin II was not due to direct inhibitions of renal tubular transport systems, but to alterations of renal hemodynamics which may partly be mediated by the adenosine receptor.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.81-89
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• 1992

Enuresis is a common voiding disorder among children. There are several therapeutic regimens for the disorder available today; behavioral therapies, psychotherapy, bladder training, sleep interruption, hypnosis and drug therapy. Recently, the efficacy of drug therapy has been acknowledged, particularly of antidepressants. Among the tricyclic antidepressants, imipramine is most frequently employed for the treatment of enuresis. Present study was undertaken to investigate the mechanism of imipramine on the contractility of urinary bladder in relation to the calcium modulation using isolated strips of rat detrusor urinae. 1. The electric fileld stimulation-induced contraction was abolished by imipramine, but partially inhibited by atropine. 2. Imipramine reduced the basal tone and diminished the phasic activity of detrusor muscle concentration-dependently, which was similar to that of diltiazem, a calcium channel blocker. 3. Imipramine suppressed the maximal responses and shifted the concentration-response curves of bethanechol and ATP to right. 4. Imipramine inhibited the calcium-induced recovery of tension in calcium-free physiologic salt solution (PSS) with a mode of action similar to that of diltizaem. 5. A23187, a calcium ionophore recovered the basal tone which had been reduced by imipramine in normal PSS. 6. In calcium-free PSS, A23187 could recover the abolished basal tone with the pretreatment of imipramine, but it exerted a partial recovery with the pretreatment of TMB-8, an inhibitor of intracellular calcium release. Based on these results, it is suggested that the inhibitory action of imipramine on the detrusor muscle exerted in part by blockade of the muscarinic and purinergic receptors, and interference with the influx of extracellular calcium, but not with the release of intracellular stored calcium, is involved in its mechanism of action.

• Journal of Yeungnam Medical Science
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• v.9 no.2
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• pp.382-395
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• 1992

GABA is an inhibitory neurotransmitter in central nervous system and produce sedative, antianxiety and muscle reaxing effects via $GABA_A$ receptor or $GABA_B$ receptor. Recently it is known that GABA is widely distributed throughout peripheral organs and may playa physiological role in certain organ. The vas deferens is innervated by species-difference. These study, therefore, was performed to investigate the mode and the mechanism of action of GABA on the norepiniphrine-, ATP- and electric stimulation-induced contraction of vas deferens of rat. Sprague-Dawley rats were sacrificed by cervical dislocation. The smooth muscle strips were isolated from the prostastic portion and were mounted in the isolated muscle bath. PSS in the bath was aerated with 95/5%-$O_2/CO_2$ at $33^{\circ}C$. Muscle tensions were measured by isometric tension transducer and were recorded by biological recording system. 1. GABA, muscimol, a $GAB_A$ agonist, and baclofen, a $GABA_B$ agonist inhibited the electric field stimulation(EFS, 0.2Hz, 1mSec, 80 V, monophasic square wave)-induced contraction with a rank order of potency of GABA greater than baclofen greater than muscimol. 2. The inhibitory effect of GABA was antagonized by delta aminovaleric acid(DAVA), a $GABA_B$ antagonist, but not by bicuculline, a $GABA_A$ mtagonist. 3. The inhibitory effect of baclofen was antagonized by DAVA, but the effect of muscimol was not antagonized by bicuculline. 4. Exogenous norepinephrine(NE) and ATP contracted muscle strip concentration dependently, but the effect of acetylcholine was negligible : and GABA did not affect the NE-and ATP-induced contractions. 5. GABA, baclofen and muscimol did not affect basal tone, and GABA did not affect the NE-and ATP-induced contractionsm 6. EFS-induced contraction was including 2 distinctable components. The first phasic component was inhibited by beta gamma-methylene ATP(mATP), a desensitizing agent of APT receptor and the second tonic component was reduced by pretreatment of reserpine(3 mg/Kg, IP). 7. GABA inhibited the EFS-induced contraction of reserpinized strips, but not the mATP-treated strips. These results suggest that in the prostatic portion of the rat vas deferens, adrenergic and purinergic neurotransmissions are exist, and GABA inhibits the release of ATP via presynaptic $GABA_B$ receptor on the excitatory neurons.

• The Korean Journal of Pharmacology
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• v.1 no.1 s.1
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• pp.17-36
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• 1965

Besides it's all important analgesic action, morphine has, among others, hyperglycemic effect, though not important clinically, which is believed to be resulted from augmented glycogenolysis in the liver and muscles due to the increased liberation of epinephrine from the adrenal medulla upon the stimulation of the posterior part of hypothalamus. It is known that adrenergic blocking agents are acting inhibitory to this sort of hyperglycemia. Much, however, should as yet be studied for the drugs which affect central nervous system and release of endogenous catecholamine as far as their effects on hyperglycemia are concerned. Much is still not known about the effect of ginseng, which has been highly regarded in the Herb Medicine, as far as it's influence on the blood sugar is concerned. Author investigated the effects of chlorpromazine, reserpine and ginseng on epinephrine induced, and morphine-induced hyperglycemiae. Animals used in this experiment were healthy albino rabbits weighing approximately 2.0 kg of body weight and were all fasted for 24 hours, before the experiment undertaken. Blood sugar determination was carried out by Nelson-Somogy method. Results obtained are summarized as follows; 1. The groups of rabbits administered intravenously with epinephrine 0.02 mg/kg, and 0.05 mg/kg, showed marked and transient hyperglycemia within 15 minutes after injection. The maximal rate of elevation in blood sugar to the control level, were 28% and 57% respectively. The blood sugar returned to the control level within 3 hours. Thus, the hyperglycemic responses were paralleled with epinephrine doses. 2. The hyperglycemic responses by morphine were different according to the doses. The groups of rabbits in which 4 mg/kg of morphine was administered, did not show any hyperglycemic effect, but, in which 10 mg/kg of morphine administered, showed severe hyperglycemic effect, resulting in the maximal level within 2 hours after injection. The maximal rate of increasing in blood sugar ,level was 88%. Compared .with epinephrine-injected groups, morphjne-injected groups showed more persistent hyperglycemic effect, but returned to control blood sugar .level in 6 hours after injection. 3. The intravenous injection of chlorpromazine 2 mg/kg and 8 mg/kg evoked a slight, and persistent hyperglycemia. The maximal rate of increasing in blood sugar level were 15% and 23% respectively. These hyperglycemia gradually returned to the normal level in 5 or 6 hours after injection. Thus, the intensity of response was paralleled with the dose of chlorpromazine. 4. The intravenous injection of reserpine 0.2 mg/kg and 0.5mg/kg, showed the most persistent but steady elevation of blood sugar level in this experiments, resulting in the maximal level in 5 hours after injection. The maximal rate of increasing of blood sugar level were 18% and 39% respectively. 5. The blood sugar level from 24 hours to 30 hours after intraperitoneal administration of reserpine 1.0mg/kg, did not show statistically significant difference, compared with control groups. 6. The oral administration of ginseng extract 15 ml/kg did not. show any :change in blood sugar level. 7. The intravenous administration of epinephrine 0.05 mg/kg or morphine 4 mg/kg to the group pretreated with ginseng extract 15 ml/kg $20{\sim}30$ minutes before the experiment, evoked more marked hyperglycemic effect than the non-pretreated group. 8. The intravenous administration of epinephrine 0.02 mg/kg, morphine 4 mg/kg, or morphine 10 mg/kg to the groups pretreated with reserpine 0.2 mg/kg or 0.5 mg/kg $20{\sim}30$ minutes before experiment, produced more marked and persistent hyperglycemic effects than the groups injected with single epinephrine or morphine injection. 9. When epinephrine 0.05 mg/kg or morphine 10 mg/kg administered intravenously to the groups pretreated with the intraperitoneal administration of reserpine 1 mg/kg 24 hours before experiment morphine-induced hyperglycemia was inbibited, but epinephrine-induced hyperglycemia was augmented. 10. When epinephrine 0.05mg/kg or morphine 10 mg/kg administered intravenously to the groups pretreated with chlorpromazine, 2 mg/kg, 4 mg/kg, and 8 mg/kg $20{\sim}30$ minutes before the experiment, morphine-induced hyperglycemia was inbibited, but epinephrine-induced hyperglycemia was more persistent.