• 제목/요약/키워드: $[^3H]$ yohimbine

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Dopamine이 토끼 유두근의 수축력과 활동전압에 미치는 영향 (Effects of Dopamine on the Contractility and Action Potential of the Rabbit Papillary Muscle)

  • 허인회;박종완
    • 약학회지
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    • 제32권6호
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    • pp.402-414
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    • 1988
  • In order to clarify the receptor types and mechanisms underlying the positive inotropic effect of dopamine on the mammalian ventricular myocardium, the action potential, its first derivatives and isometric contraction of the rabbit papillary muscle were recorded using a force transducer and glass capillary microelectrodes filled with 3M KCl. The results were as follows; (1) In normal Tyrode solution, the contractile force was increased and duration of action potential was shortened with increments of dopamine concentration ($10^{-6}-10^{-4}M$). (2) The dose-response curve was markedly shifted to the right by pretreatment with reserpine (5mg/kg i.p., 24hrs prior to the experiment). (3) In 19mM $K^+-Tyrode$ solution, the duration of action potential, maximum rate of rise (V_{max}) of action potential and overshoot were significantly increased with increments of dopamine concentration ($10^{-6}-10^{-4}M$). (4) The inotropic effect of dopamine on the rabbit papillary muscle pretreated with reserpine was antagonized by atenolol ($10^{-6}M$), but not by phentolamine ($3{\times}10^{-6}M$). (5) In rabbit papillary muscle partially depolarized by 19mM $K^+-Tyrode$ solution, slow electrical response (calcium mediated action potential) as well as contraction were restored by dopamine ($10^{-4}M$); this restoration was blocked by calcium antagonists ($3{\times}10^{-5}M$ $LaCl_3{\cdot}6H_2O$, $3{\times}10^{-6}M$ diltiazem) or ${\beta}-adrenoceptor$ antagonist ($3{\times}10^{-6}M$ atenolol), but not affected by ${\alpha}-adrenoceptor$ antagonist ($10^{-5}M$ phentolamine, $3{\times}10^{-6}M$ yohimbine) or vascular dopaminergic receptor antagonist ($10^{-5}M$ haloperidol). The above results may be interpreted as that the positive inotropic effect of dopamine through both direct and indirect action are caused by increase in slow inward current ($Ca^{2+}$ influx into themyocardial cell), and the direct action is mainly due to the stimulation of ${\beta}-adrenoceptors$ in the rabbit papillary muscle.

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초대배양한 토끼 신장 근위세뇨관세포의 Na+ uptake에 대한 norepinephrine 과 angiotensin II의 상호작용 (Interaction between norepinephrine and angiotensin II on Na+ uptake in primary cultured rabbit renal proximal tubule cells)

  • 박수현;고현주;한호재
    • 대한수의학회지
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    • 제38권3호
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    • pp.525-534
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    • 1998
  • 신장 근위세뇨관세포들은 사구체에서 여과된 물질의 재흡수, 분비 및 대사에 관여하는 여러 호르몬들의 수용체들을 가지고 있다. 이들중에서 norepinephrine(NE)과 angiotensin II(ANG II)는 $Na^{+}/H^+$ 상호운반계를 조절함으로써 혈압조절에 관여하는 것으로 알려져 있으나 이들의 상호관계에 대해선 연구보고가 많지 않다. 본 연구는 초대배양한 토끼신장 근위세뇨관세포를 이용한 $Na^+$ uptake 실험을 통하여 NE이 어떠한 수용체를 통하여 $Na^{+}/H^+$ 상호운반계를 조절하는지 그리고 이러한 작용에 있어서 NE과 ANG II의 상호관계를 알아보고자 실시하였다. NE(>$10^{-9}M$)은 $Na^+$ uptake를 유의성 있게 증가시켰다($10^{-9}M$ NE : $27{\pm}4%$ increase vs. Control;p < 0.05). $\alpha$ 길항제(phentolamine, $10^{-10}M$)는 NE($10^{-9}M$)에 의해 유도된 $Na^+$ uptake를 유의성 있게 차단하였으나 (phentolamine+NE : $29{\pm}5%$ inhibition vs. NE ; p〈 0.05), ${\alpha}_1$ (pra-zosin, $10^{-10}M$) 및 ${\alpha}_2$ 길항제(yohimbine, $10^{-10}M$)는 부분적으로 차단하였다. ${\beta}$ 길항제(propra-nolol, $10^{-10}M$)도 역시 NE에 의해 유도된 $Na^+$ uptake를 유의성 있게 차단하였으나(propranolol+NE : $24{\pm}6%$ inhibition vs. NE ; p< 0.05), ${\beta}_1$(atenolol, $10^{-10}M$) 및 ${\beta}_2$ 길항제(butoxamine, $10^{-10}M$)는 부분적으로 차단하였다. 이러한 결과들은 NE에 의해 유도된 $Na^+$ uptake 증가작용은 ${\alpha}$(${\alpha}_1$${\alpha}_2$ )와 ${\beta}$(${\beta}_1$${\beta}_2$) 수용체 모두를 통하여 일어난다는 것을 시사해주고 있다. ANG II($10^{-11}M$) 또는 NE(${\alpha}_1$, ${\alpha}_2$, ${\beta}_1$, ${\beta}_2$ 작동제) 단독처리군의 $Na^+$ uptake는 대조군에 비해 유의성 있게 증가하였으나 (ANG II : $23{\pm}9%$ increase vs. Control; p < 0.05), 병합처리시 상승작용은 나타나지 않았다. ${\alpha}$ 또는 ${\beta}$ 길항제 처리시 NE 및 ANG II에 의해 유도되었던 $Na^+$ uptake 증가는 유의성 있게 차단되었다(phentolamine+NE+ANG II : $25{\pm}3%$ inhibition, propranolol+NE+ANG II : $24{\pm}6%$ inhibition vs. NE+ANG II, respectively ; p〈 0.05). 이 결과들은 $Na^+$ uptake에 있어서 ${\alpha}$(${\alpha}_1$${\alpha}_2$)와 ${\beta}$(${\beta}_1$${\beta}_2$) 수용체와 ANG II의 관련성을 시사해 준다. 결론적으로 토끼 신장 근위세뇨관세포에서 NE은 ${\alpha}_1$, ${\alpha}_2$, ${\beta}_1$${\beta}_2$ 수용체를 통하여 $Na^+$+ uptake를 증가시켰으며 이들 수용체는 ANG II $Na^+$ uptake 증가작용에 관여하였다.

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Xylazine이 histamine 유리에 미치는 영향 (Effect of xylazine hydrochloride on histamine release)

  • 김영환;박준형
    • 한국동물위생학회지
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    • 제25권1호
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    • pp.53-73
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    • 2002
  • It has been reported that degranulation of mast cells in rats, rabbits and dog was observed after dosing xylazine hydrochloride(Xh) which has been widely used as sedative, analgesic and muscular relaxant. Therefore, this experiment was conducted to examine the relations between Xh and histamine release and to identify the action of ${\alpha}$-adrenoceptors which exists on the suface of mast cells. 1. The content of histamine within serum was measured with HPLC by performing the O-phthalaldehyde(OPA) fluorescent derivation. The pretreatment method had a little modification from the conventional method. The pretreament was carried out in the following method. 0.2$m\ell$ of serum and 1$m\ell$ of butanol were added to mixed together and then the liquid was centrifugally separated at 4$^{\circ}C$ and 2,000 rpm for 3 minutes. 0.4$m\ell$ of 0.1N HCl and 1.6$m\ell$ of heptane were added to 0.8$m\ell$ of supernatant taken from the liquid, and they were mixed together. This mixture was also centrifugally separated at 4$^{\circ}C$ and 2,000 rpm for 5 minutes. The supernatant was thrown away and the OPA fluorescent derivation was carried out with 0.2$m\ell$ of the lower liquid then, 5 minutes after mixing 400${\mu}\ell$ of 0.1N HCl, 120${\mu}\ell$ of 1N NaOH and 40${\mu}\ell$ of 0.1% OPA in the 0.2$m\ell$ of the lower liquid,120${\mu}\ell$ of 3.57N H$_3$PO$_4$ was added to the mixed liquid, and the liquid, was mixed again and syringe-filtered. Then, the measurement was done with HPLC in the 30 : 70(ν/ν) ratio of 0.004M KH$_2$PO$_4$: CH$_3$CN, flow rate of 1.0$m\ell$/min., and a wavelength of λex= 350nm and λem=444nm at the column temperature of 27$^{\circ}C$, using the fluorescence detector. 2. The content of histamine in each laboratory animal appeared to be higher in such an order as rabbit, rat, guinea pig, dog, Korean indigenous goat, swine, Korean indigenous cattle, Holstein, and mouse, of which the individual mean values${\pm}$standard deviation were 2.0668 ${\pm}$ 0.6049. 0.4999 ${\pm}$ 0.2278, 0.4241 ${\pm}$ 0.1974, 0.1054 ${\pm}$ 0.0556, 0.1028 ${\pm}$ 0.0276, 0.0972 ${\pm}$ 0.0513, 0.0872 ${\pm}$ 0.0373, 0.0717 ${\pm}$ 0.0379, and 0.0706 ${\pm}$ 0.0366, respectively. 3. The content of histamine was measured at the moments of 15-, 30-, 60-, 120-minutes after inoamuscular injection of 20mg/100kg Xh into two to 4 years old Holstein weighing 600∼700kg. The result showed that there was a significant increase at the times of 30- and 90-minutes after injection(p<0.05). 4. Intramuscular injection of 3mg/10kg Xh was given to crossbred pug dogs weighing 2.5∼4.3kg. The content of histamine was measured at the times of 30-, 60-, 90- and 120-minutes after injection. The result revealed that there was a significant increase at the times of 60-and 90-minutes after injection(p<0.05). 5. Intramuscular injection of 10mg/$m\ell$∼25mg/$m\ell$ Xh in concentration of 0.1$m\ell$ was applied to Korean indigenous goat over 5 months old. Then, the content of histamine was measured at the times of 15-, 30-, 60- and 90-minutes after injection. A significant increase was shown at the times of 30- and 60-minutes after injection(p<0.05). 6. The content of histamine was measured at the moments of 30- and 60-minutes after intramuscular injection of 0.1-0.2$m\ell$ Xh (20mg/$m\ell$) into male rabbits weighting 2.5-4kg. A significant increase was found at the moment of 60 minutes after injection(p<0.001). 7. After administering Xh to the mast cell taken from the abdominal cavity of mouse, the content of histamine was measured. The result showed that the higher the concentration, the more significantly the content of histamine was increased(p<0.05). 8. Compound 48/80 was administered in concentration of 5$\mu\textrm{g}$/$m\ell$ and 10$\mu\textrm{g}$/$m\ell$ to the mast cell picked from the abdominal cavity of mouse. The result showed that there was a significant increase in the content of histamine in case of the concentration of 10$\mu\textrm{g}$/$m\ell$(p<0.05). It was found to be about 10,000 to 500,000 times stronger than the Xh. 9. After premedication of 1mg/kg of yohimbine hydrochloride as ${\alpha}$$_2$-adrenergic antagonist to rabbits, the Xh was administered to them. The result was that the value of histamine within serum was decreased significantly(p<0.001). 10. After premeditation of 1mg/kg of prazosin hydrochloride as ${\alpha}$$_1$-adrenergic antagonist to rabbits, the Xh was administered to them. It was found that the value of histamine within serum was decreased significantly(p<0.005). 11, Prazosin hydrochloride and yohimbine hydrochloride as ${\alpha}$$_1$-adrenergic antagonist, respectively, and ${\alpha}$$_2$-adrenergic antagonist were administerd. In this case, the value of histamine within serum was decreased significantly(p<0.0001). As the results, when the Xh is administered to various kinds of animals, the amount of histamine release within serum is increased. In view of the results so far achieved, it is concluded that Xh acted on both a$_1$-adrenoreceptor and ${\alpha}$$_2$-adrenoreceptor induces the degranulation of mast cell.