• Journal of Ginseng Research
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• v.10 no.1
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• pp.55-65
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• 1986

Effects of various nucleotides including GMP, glnsenoslde $Rb_2$, and redoxidants on the activities of both particulate and soluble guanylate cyclase from rat brain have been studied. At the low concentra狀onto of GMP, AMP, ADP, and ATP the activity of guanylate cyclase is not substantially affected, whereas the inhibitory effects of these nucleotides on the enzyme activities are increased with the increasing concentrations of the nucleotides. Similarly, the activity of the soluble guanylate cyclase is inhibited with the increasing concentrations of the nucleotides. Inhibitory effects of GMP, AMP, ADP, and ATP on the activities of particulate guanylate cyclase and soluble guanylate cyclase is reduced in the presence of ginsenoside $Rb_2$. It is apparent broom this finding that there are seperate binding sites on the guanylate cyclase molecule specific for nucleootides and for ginsenoside $Rb_2$. $NAD^+$ shows no significant effect on the activities of particulate guanylate cyclase, whereas NADH inhibits the activities of the enzyme. The activity of particulate guanylate cyclase is slightly inhibited by iodine, whereas that of soluble gllanylate cyclase is strongly inhibited.

• The Korean Journal of Pharmacology
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• v.25 no.1
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• pp.59-66
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• 1989

To determine the relation between cGMP and ion reabsorption in rat medullary thick ascending limb of Henle's loop (mTALH) the effects of loop diuretics, furosemide and ethacrynic acid, on the guanylate cyclase of rat mTALH were investigated. The interactions between loop diuretics and cyclooxygenase inhibitors, aspirin and indomethacin, on guanylate cyclase of rat mTALH were also investigated. Furosemide and ethacrynic acid increased guanylate cyclase activity and these effects were not inhibited by aspirin or indomethacin. Arachidonic acid potentiated the stimulatory effect of furosemide on guanylate cyclase. These results suggest that furosemide and ethacrynic acid activate guanylate cyclase directly, and in addition, furosemide affects indirectly via prostaglandin. The reabsorption of sodium chloride may be, at least partially, controlled by cGMP in mTALH.

• The Korean Journal of Zoology
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• v.36 no.3
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• pp.433-438
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• 1993

In the previous paper (Choi et al., 1992), we found that a large but transient elevation in intracellular cGMP levels occur concomitant with the myoblast fusion. To establish the physiological significance of the elevation of cGMP levels, the change in guanylate cyclase activity dudng myoblast fusion and the correlation hetween various chemicals that may affect guanylate cyclase adivity and myoblast fusion were examined. Sodium nitroprusside, a nitric oxide-forming compound, induced a precocious fusion and increased guanylate cyclase activity compared to the control. Furthermore, L-NG-monomethyl arginine, specific inhibitor of L-arginine: nitric oxide synthase, inhibited the cell fusion in a dose-dependent manner, without affecting biochemical differentiation. On the basis of our present findings, we propose that the onset of myoblast fusion is somehow correlated with the rise in cellular cGMP levels that is regulated by the activation or inhibItIon of soluble guanylate cyclase, via as yet undefined mechanism but possibly through L-arginine: nitric oxide pathway.

• Journal of Ginseng Research
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• v.7 no.2
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• pp.148-155
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• 1983

The effects of the five ginsenosides on the activities of particulate adenylate cyclase and particulate guanylate cylase of rat brain have been studied. The range of concentrations of ginsenosides were between 10$\mu\textrm{g}$ and 500$\mu\textrm{g}$ per 500${mu}ell$ reaction mixture, Also, the effects of three ginsenosides on the activity of soluble guanylate cylace have been studied in the same range of concentrations as in particulate adenylate cyclase. Only ginsenoside Re has shown the reciprocal feeects when tested with particulated adenylate cyclase and particulate guanylated cyclase. Regulatory action of the several mononucleotides on the activities of adenylate cyclase and guanylate cyclase was examined. Ginsenoside Rd-inhibited adenylate cyclase was activated in great extent by the addition of increasing amount of GMP. On the other hand, ginsenoside Rc-activated guanylate cyclase was inhibited by the addition of increasing amount of AMP and GMP. The fact that the stimulatory action of GMP is observed only with particulated adenylate cyclase but not with soluble suanylate cyclase suggests that the action is membrane-related one. The competitive action was observed between ginsenoside Rb2 and dopamine in their binding to the receptors. This result is clear-cut evidence that the ginsenoside Rb2 binds specifically to $\beta$-adrenergic receptors.

• Biomolecules & Therapeutics
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• v.13 no.1
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• pp.35-40
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• 2005

This study was performed to investigate the regulatory mechanism of cerebral blood flow of adenosine A$_{2B}$ receptor agonist in the rats, and to define whether its mechanism is mediated by adenylate cyclase, guanylate cyclase and potassium channel. In pentobarbital-anesthetized, pancuronium-paralyzed and artificially ventilated male Sprague-Dawley rats, all drugs were applied topically to the cerebral cortex. Blood flow from cerebral cortex was measured using laser-Doppler flowmetry. Topical application of an adenosine A$_{2B}$ receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA; 4 umol/I) increased cerebral blood flow. This effect of NECA (4 umol/I) was not blocked by pretreatment with adenylate cyclase inhibitor, MDL-12,330 (20 umol/I). But effect of NECA (4 umol/I) was blocked by pretreatment with guanylate cyclase inhibitor, LY-83,583 (10 umol/I) and pretreatment with ATP-sensitive potassium channel inhibitor, glipizide (5 umol/I). These results suggest that adenosine A$_{2B}$ receptor increases cerebral blood flow. It seems that this action of adenosine A$_{2B}$ receptor is mediated via the activation of guanylate cyclase and ATP-sensitive potassium channel in the cerebral cortex of the rats.

• The Korean Journal of Pharmacology
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• v.22 no.2
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• pp.128-134
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• 1986

To determine the relationship between hydrochlorothiazide-induced diuretic action and cyclic nucleotides, the effects of hydrochlorothiazide (5 mg/kg, i.v.) on the renal tissue level of cyclic nucleotides and the renal adenylate cyclase and guanylate cyclase activity were investigated. Hydrochlorothiazide elecitied the maximal diuretic effect between 10 and 20 min after the injection of drug. The increased urine flow and urinary electrolytes excretion returned to the control levels 60 min after the injection of drug. 5 and 15 min after drug administration the cAMP level of renal tissue was significantly decreased, but 60 min after the cAMP level was not different from the control level. The cGMP level of renal tissue was not affected by hydrocholorothiazide. Hydrochlorothiazide $(5\;{\times};10^{-4}\;M)$ inhibited the renal adenylate cyclase but not affected the renal guanylate cyclase. These results suggest that cAMP may be involved in the renal action mechanism of hydrochlorothiazide and the involvement of cGMP is uncertain.

• Biomolecules & Therapeutics
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• v.12 no.2
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• pp.108-113
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• 2004

This study was performed to investigate the regulatory mechanism of cerebral blood flow of adenosine $A_{2B}$ receptor agonist in the rats, and to define whether its mechanism is mediated by adenylate cyclase and guanylate cyclase. in pentobarbital-anesthetized, pentobrabital-paralyzed and artificially ventilated male Sprague-Dawley rats, all drugs were applied topically to the cerebral cortex. Blood How from cerebral cortex was measured using laser-Doppler flowmetry. Topical application of an adenosine $A_{2B}$ receptor agonist, 5'-N-ethylcar-boxamidoadenosine (NECA; 4 umol/l) increased cerebral blood flow. This effect of NECA (4 umol/l) was not blocked by pretreatment with adenylate cyclase inhibitor, MDL-12330 (20 umol/l). But effect of NECA (4 umol/l) was blocked by pretreatment with guanylate cyclase inhibitor, LY-83383 (10 umol/l). These results suggest that adenosine $A_{2B}$ receptor increases cerebral blood flow. It seems that this action of adenosine $A_{2B}$ receptor is mediated via the activation of guanylate cyclase in the cerebral cortex of the rats.

• Biomolecules & Therapeutics
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• v.13 no.2
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• pp.95-100
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• 2005

This study was performed to investigate the mechanism of cerebral blood flow of adenosine $A_{2B}$ receptor agonist in the rats, and to define whether its mechanism is mediated by nitric oxide (NO) and guanylate cyclase. In pentobarbital-anesthetized, pancuronium-paralyzed and artificially ventilated male Sprague-Dawley rats, all drugs were applied topically to the cerebral cortex. Blood flow from cerebral cortex was measured using laser-doppler flowmetry. Topical application of an adenosine $A_{2B}$ receptor agonist, 5'-N-ethylcar-boxamidoadenosine (NECA; $4{\mu}mol/l$) increased cerebral blood flow. This effect of NECA ($4{\mu}mol/l$) was blocked by pretreatment with NO synthase inhibitor, $N^G$-nitro-L-argine methvlester (L-NAME; $40{\mu}mol/l$) and guanylate cyclase inhibitor, LY-83,583 ($10{\mu}mol/l$). These results suggest that adenosine $A_{2B}$ receptor increases cerebral blood flow. It seems that this action of adenosine $A_{2B}$ receptor is mediated via the NO and the activation of guanylate cyclase in the cerebral cortex of the rats.

• Journal of Ginseng Research
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• v.7 no.2
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• pp.95-101
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• 1983

The effect of ginsenosides on the adenylate cyclase and guanylate cyclase of rat brain has been studied. We have found that Rbl, Rc and one unknown ginsenoside (probably Ra) exerted reciprocal effects on adenylate cyclase and guanylate cyclase. This dual effect of ginsenosides leads us to speculate that some ginsenosides may act as regulatory agents and modulate the activities of these two enzyme systems.

• Biomolecules & Therapeutics
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• v.12 no.2
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• pp.68-73
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• 2004

This study was performed to investigate the regulatory mechanism of cerebral blood How of adenosine $A_2$ receptor agonist in the rats, and to define whether its mechanism is mediated by nitric oxide (NO), adenylate cyclase and guanylate cyclase. In pentobarbital-anesthetized, pancuronium-paralyzed and artificially ventilated male Sprague-Dawley rats, all drugs were applied topically to the cerebral cortex. Blood flow from cerebal cortex was measured using laser-Doppler flowmetry. Topical application of an adenosine $A_2$ receptor agonist [5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA; 4 umol/l)] increased cerebral blood flow. This effect of CPCA (4 umol/l) was blocked by pretreatment with NO synthase inhibitor [$N^G$-nitro-L-argine methylester (L-NAME; 140 umol/l)] and adenylate cyclase inhibitor [MDL-12,330 (20 umol/l)]. But the effect of CPCA (4 umol/l) was not blocked by pretreatment with guanylate cyclase inhibitor [LY-83,583 (10 umol/l)]. These results suggest that adenosine $A_2$ receptor increases cerebral blood How. It seems that this action of adenosine $A_2$ receptor is mediated via the NO and the activation of adenylate cyclase in the cerebral cortex of the rats.