• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.63-74
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• 1995

It has been known that, during hypoxia, the adrenal medulla is activated to release catecholamines (CA) while hypoxia also inhibits high $K^+$ -induced CA secretion in the cultured bovine adrenal chromaffin cells. The present study was attempted to examine the effect of hypoxia on CA secretion evoked by chlinergic stimulation and membrane-depolarization from the isolated perfused rat adrenal glands and also to clarify its mechanism of action. For this purpose, using the isolated rat adrenal glands, the effects of hypoxia on CA release evoked by nicotinic ($N_1$) and muscarinic ($M_1$) receptor agonists, membrane-depolarizing agent, $Ca^{++}$-channel activator, intracellular $Ca^{++}$-releaser and ACh were determined. Experiments were carried out, perfusing Krebs solution pre-equilibrated with a gas mixture of 95% N_2$ and 5% $CO_2$. Hypoxia was maintained for $3{\sim}4$ hours through the experiments. Hypoxia gradually caused a time-dependent seduction in CA secretion evoked by DMPP ($100{\mu}M$), McN-A-343 ($100{\mu}M$), ACh (5.32 mM), Bay-K-8644 ($10{\mu}M$) and high $K^+$ (56 mM) respectively. How-ever, it did not affect CA secretion evoked by cyclopiazonic acid ($10{\mu}M$). Hypoxia itself also did fail to produce any influence on spontaneous secretory response of CA. These experimental results suggest that hypoxia depresses CA release evoked by both cholinergic stimulation and membrane-depolarization from the isolated rat adrenal medulla, and that this inhibitory activity may be due to the result of the direct inhibition of $Ca^{++}$ influx into the chromaffin cells without any effect on the calcium mobilization from the intracellular store.

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.16-22
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• 1993

Background: The Microbicidal and cytotoxic activities of neutrophils are to a large extent dependent on a burst of oxidative metabolism which generates superoxide anion, hydrogen peroxide, and other reactive products of oxygen. The respiratory burst of PMN is initiated by intracellular calcium mobilization that follows immune or particular stimulation and is very sensitive to modulation by c-AMP or adenosine. Despite its antagonism against adenosine, earlier study has demonstrated potent theophylline inhibition of the PMN respiratory burst at variable ranges of blood concentrations of theophylline in the healthy normal volunteers and in the septic animals pretreated or early post-treated with aminophylline (AMPH) or pentoxifylline. However it is unclear whether theophylline inhibits the superoxide generation or not in the established human sepsis caused by acute pneumonia, as taking into consideration of the fact that full activation of neutrophils have occurred within minutes after the septic insult in the animal experiments. Methods: We measured the $O_2$ generation of peripheral arterial neutrophils obtained from 11 human septic subjects caused by acute pneumonia before and 1 hour after completion of continuous AMPH infusion. Patients were identified and studied within 48 hour of admission. All subjects were administered an intravenous loading and maintenance dose of AMPH. The generation of $O_2$ was measured at a discrete time point (60 min) by the reduction of ferricytochrome c.PMA (10 ${\mu}g/ml$) was used as a stimulating agent. PMNs were isolated at a concentration of $2{\times}10^6$ cells/ml. The arterial oxygen tension, blood pressure and heart rates were also checked to evaluate the systemic effects of AMPH in the acute pneumonia. Results: The mean serum concentration of AMPH at 60 minutes was $8.8{\pm}0.6{\mu}g/ml$. Sixty minutes after AMPH infusion the generatition of $O_2$ was decreased from $0.076{\pm}0.034$ to $0.013{\pm}0.004$(OD) (p<0.05) and from $0.177{\pm}0.044$ to $0.095{\pm}0.042$(OD) (p<0.01) in the resting and stimulated PMNs respectively. $PaO_2$ was not changed after AMPH infusion. Conclusion: AMPH may compromise host defense by significant inhibition of neutrophil release of superoxide anion and it had no effect on improving $PaO_2$ in the acute pneumonia.

• The Korean Journal of Pharmacology
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• v.14 no.1_2
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• pp.33-40
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• 1978

1) The authors studied the effect of increasing age on the contraction and relaxation mechanism in the ureteral smooth muscle of the guinea pig. 2) Two to three week old, three month old, and two to three year old guinea pig ureters were used and the consistent amplitude of contratile responses were induced by using train stimulation. 3) After mounting the specimens in Tyrode's solution containing 2.6mM $Ca^{++}$, the ureter was stimulated, of which amplitude was initial contraction and next continuously superfused with $Ca^{++}$-free Tyrod's solution. When the contractile response stopped by electrical field stimulation, the muscle specimens was superfused with Tyrode's solution 0.25mM $Ca^{++}$ for 15min and stimulated with the same parameters. Thereafter, the contraction of $Ca^{++}$ in the solution was increased step by step up to 2.7mM. 4) The ureters of 2-3 week old guinea pigs needed less $Ca^{++}$ for the recovery of contractile response than those of three month and two to three year old did. In 2.7mM $Ca^{++}$, the ureters of 2-3 week and 3 month old guinea pigs recovered the contractile response of over 90% but those of 2-3 year old recovered the contractility of 77.2%. 5) Isoproterenol inhibited in dose dependent manner from $10^{-7}$ to $10^{-5}\;M$ ureteral contractility of both 2-3 week and 2-3 year old guinea pigs. The inhibition of the old ureter by isoproterenol was significantly less (P<0.025) than that of the younger ureter. However theophylline showed the strong inhibition independent of the function of age. 6) Dibutyryl cyclic AMP showed dose-dependent inhibition of the contraction of ureters of 2-3 week old guinea pigs but there was shown no inhibition in the old ureters. Further, the content of endogenous cyclic AMP in the two week old ureter was higher by 73% than that of 17 month old ureter. Cyclic GMP contents was not much different between two groups. 7) The ureteral smooth muscle of the younger guinea pig had more efficiency than that of the older animals in the mobilization and storage of calcium which concerned itself in the contraction and relaxation mechanism.