• 대한수의학회지
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• 제25권1호
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• pp.33-40
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• 1985

The inhibitory action of oxymetazoline on the spontaneous movements of isolated intestinal strips of the rabbit and the effects of antagonists upon the oxymetazoline actions were assessed with recordings through both isometric and isotonic transducers, and comparisons were made between both methods of recording. There were significant differences between the slopes of regression equations calculated from log dose response curves of oxymetazoline obtained from jejunum and those from ileum. But no difference was noted between both recordings either through isotonic transducer or through isometric transducer. The $ID_{50}$ of oxymetazoline obtained from the recording through isotonic transducer was $6.31{\times}10^{-7}M$ in jejunum and $3.16{\times}10^{-8}M$ in ileum. The recording through isometric transducer gave the values of $5.01{\times}10^{-7}M$ in jejunum and $1.07{\times}10^{-8}M$ in ileum. The $pA_2$-values of prazosin to oxymetazoline calculated from the recording through isotonic transducer were 8.13 in jejunum and 8.31 in ileum and the recording through isometric transducer gave the values of 7.29 and 8.26 in jejunum and ileum, respectively. The $pA_2$-values of phentolamine to oxymetazoline obtained from the recording through isotonic transducer were 8.18 in Jejunum and 9.31 in ileum and those from the recording through isometric transducer were 7.75 and 8.13 in jejunum and ileum, respectively. These results indicate that there are no significant differences between recordings either through isotonic transducer or through isometric transducer in assessing inhibitory responses of intestinal movement to certain drugs.

• The Korean Journal of Physiology and Pharmacology
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• 제27권4호
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• pp.325-331
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• 2023

α₁-adrenoceptors link via the G-protein Gq/G₁₁ to both Ca²⁺ entry and release from stores, but may also activate Rho kinase, which causes calcium sensitization. This study aimed to identify the subtype(s) of α₁-adrenoceptor involved in Rho kinase-mediated responses in both rat aorta and mouse spleen, tissues in which contractions involve multiple subtypes of α₁-adrenoceptor. Tissues were contracted with cumulative concentrations of noradrenaline (NA) in 0.5 log unit increments, before and in the presence of an antagonist or vehicle. Contractions produced by NA in rat aorta are entirely α₁-adrenoceptor mediated as they are competitively blocked by prazosin. The α_1A-adrenoceptor antagonist RS100329 had low potency in rat aorta. The α_1D-adrenoceptor antagonist BMY7378 antagonized contractions in rat aorta in a biphasic manner: low concentrations blocking α_1D-adrenoceptors and high concentrations blocking α_1B-adrenoceptors. The Rho kinase inhibitor fasudil (10 µM) significantly reduced aortic contractions in terms of maximum response, suggesting inhibition of α_1B-adrenoceptor mediated responses. In the mouse spleen, a tissue in which all 3 subtypes of α₁-adrenoceptor are involved in contractions to NA, fasudil (3 µM) significantly reduced both early and late components to the NA contraction, the early component involving α_1B- and α_1D-adrenoceptors, and the late component involving α_1B- and α_1A-adrenoceptors. This suggests that fasudil inhibits α_1B-adrenoceptor mediated responses. It is concluded that α_1D- and α_1B-adrenoceptors interact in rat aorta and α_1D-, α_1A- and α_1B-adrenoceptors interact in the mouse spleen to produce contractions and these interactions suggest that one of the receptors preferentially activates Rho kinase, most likely the α_1B-adrenoceptor.

• The Korean Journal of Pain
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• 제37권1호
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• pp.26-33
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• 2024

Background: Sitagliptin is an antidiabetic drug that inhibits dipeptidyl peptidase-4 enzyme. This study aimed to investigate the antinociceptive and anti-inflammatory effects of sitagliptin in formalin and carrageenan tests and determine the possible mechanism(s) of its antinociceptive activity. Methods: Male Swiss mice (25-30 g) and male Wistar rats (180-220 g) were used for formalin and carrageenan tests, respectively. In the formalin test, paw licking time and in the carrageenan test, paw thickness were considered as indexes of pain behavior and inflammation respectively. Three doses of sitagliptin (2.5, 5, and 10 mg/kg) were used in these tests. Also, several antagonists and enzyme inhibitors were used to evaluate the role of adrenergic, serotonergic, dopaminergic, and opioid receptors as well as the NO/cGMP/K_ATP pathway in the antinociceptive effect of sitagliptin (5 mg/kg). Results: Sitagliptin showed significant antinociceptive and anti-inflammatory effects in the formalin and carrageenan tests respectively. In the carrageenan test, all three doses of sitagliptin significantly (P < 0.001) reduced paw thickness. Pretreatment with yohimbine, prazosin, propranolol, naloxone, and cyproheptadine could not reverse the antinociceptive effect of sitagliptin (5 mg/Kg), which indicates that adrenergic, opioid, and serotonin receptors (5HT₂) are not involved in the antinociceptive effects. L-NAME, methylene blue, glibenclamide, ondansetron, and sulpiride were able to reverse this effect. Conclusions: NO/cGMP/K_ATP, 5HT₃ and D₂ pathways play an important role in the antinociceptive effect of sitagliptin. Additionally significant anti-inflammatory effects observed in the carrageenan test might contribute in reduction of pain response in the second phase of the formalin test.

• 대한약리학회지
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• 제31권1호
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• pp.39-51
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• 1995

갑상선 기능 항진증 심장에서의 ${\beta}-adrenoceptor$의 역할은 잘 알려져 있으나 ${\alpha}-adrenoceptor$에 대해서는 알려져 있지 않은 바, 저자 등은 갑상선 기능 항진증 기니픽 심장의 유두근에서 일반 미세 전극과 이온-선택적 미세 전극을 이용하여 세포내 $Na^+$과 $H^+$ 활성도에 대한 phenylephrine의 영향을 연구하였다. Phenylephrine ($10^{-5}$ 또는 $3{\times}10^{-5}M$)에 의한 ${\alpha}_1-adrenoceptor$ 자극은 다양한 활동전위의 변동, 수축기 막전위의 과분극 ($1.5{\pm}0.1mM$), 세포내 활성도 증가 ($0.4{\pm}0.15mM$), 현저한 수축력 증가 ($220{\pm}15%$) 그리고 세포내 pH의 증가 ($0.06{\pm}0.002\;unit$)를 일으켰고, 이와 같은 변동이 prazosin과 atenolol에 의해 차단되었다. 그래서 이들 효과가 ${\alpha}_1-adrenoceptor$를 경유함을 알 수 있었고, 역시, 세포내 $Na^+$ 활성도와 수축력 증가 효과가 $Na^{+}-H^{+}$ 교환기 억제제인 ethylisopropylamiloride로 차단됨으로 보아 ${\alpha}_1-adrenoceptor$ 자극은 $Na^{+}-H^{+}$ 교환기를 자극하여 세포내 $a^{i}_{Na}$와 pH를 증가시킴을 시사한다. 이는 ${\alpha}_1-adrenoceptor$ 자극에 의한 세포내 $Na^+$감소와 초기 수축력 감소 효과를 나타내는 정상 기니픽 심장과는 매우 다른 결과로 갑상선 기능 항진증 심장에서 ${\alpha}_1-adrenoceptor$는 매우 중요한 기능을 갖고 있음을 의미한다.

• 대한약리학회지
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• 제26권1호
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• pp.13-23
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• 1990

가토흉부대동백근에서 MeB와 gentian violet는 용량-의존성 수축반응을 일으켰으나 evans blue와 eosine yellowish는 전혀 수축반응을 일으키지 못하였다. MeB는 돼지 장간막 동맥에서도 용량-의존성 수축반응을 일으켰다. 양표본에서 MeB $10^{-4}$ M의 단회투여는 수축반응에 이어 이완반응이 나타나는 양상성 반응을 일으켰으나, tyramine은 지속적인 수축반응을 일으켰다. Tyramine의 수축반응은 반복적이었으나 MeB의 그것은 일차 수축반응후 $3{\sim}5$시간후까지도 반복되지 않았다. Tyramine $10^{-4}$ M의 최대 수축반응 상태에서 MeB $10^{-4}$ M의 추가투여는 현저한 추가수축반응을 일으켰으나 반대로 MeB의 최대수축반응 상태에서 tyramine의 추가투여는 그이상의 수축반응을 일으키지 못하였다. Tyramine과 MeB 수축반응은 교감신경계 악물로 소실 또는 유의하게 억제되었다. Tyramine 수축반응은 MeB 수축보다 guanethidine과 6-hydroxydopamine에 더 예민한 반면, $Ca^{2+}-free$ PSS와 reserpine에 대하여는 MeB 수축반응이 tyramine 수축보다 더 예민하였고 prazosin하에서는 두 수축반응이 비슷하게 억제되었다. MeB 수축반응은 6-hydroxydopamine으로 유의하게 억제는 되었으나 소실되지 않았고, MeB 수축반응 관찰후에는 tyramine 뿐만아니라 6-hydroxydopamine의 수축반응도 소실되었다. 이상의 성적은 가토흉부대동맥과 돼지 장간막동맥에서 MeB 수축반응은 부분적으로 세포외 calcium 의존성이고 adrenaline성 신경발단으로부터의 norepinephrine유리에 기인하며, MeB의 norepinephrine유리 및 고갈작용이 tyramine 또는 6-hydroxydopamine의 작용보다 더 강력함을 시사하고 있다.

• 대한약리학회지
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• 제20권2호
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• pp.15-21
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• 1984

Clonidine으로 고혈압을 치료시 부작용으로 진정작용이 심하게 나타나며 이는 Clonidine이 중추 ${\alpha}_2$-수용체를 흥분시켜서 일으킨 결과임이 보고되었다. 본 실험에서는 부화 $1{\sim}2$일이 된 병아리에 ${\alpha}_2$-수용체 효현제들을 주사하여 정좌반사가 소실될 때까지의 시간 및 수련시간을 관찰하였으며, 그리고 guanabenz 유도 수면에 대한 ${\alpha}_1$- 및 ${\alpha}_2$-수용체 길항제 및 opiate수용체 길항제가 어떻게 관여하는 지를 검토하고 다음과 같이 요약하였다. 1) ${\alpha}_2$-수용체 효현제중 guanabenz, clonidine, guanfacine 및 B-HT 933은 용량에 의존해서 정좌반사소실까지의 잠복시간을 감소시켰다. 그러나 B-HT 920 및 oxymetazoline은 잠복시간을 경미하게 연장시켰다. 2) ${\alpha}_2$-수용체 효현제들은 용량에 비례해서 수면시간을 증가시켰고 이들의 강도는 guanabenz>clonidine>oxymetazoline${\geq}$B-HT 933${\geq}$B-HT 920> guanfacine의 순위이었다. 3) ${\alpha}_2$-수용체 길항제들은 양에 비례해서 guanabenz 유도 수면시간을 감소시켰으며 이들의 강도는 yohimbine>rauwolscine>piperoxan${\geq}$RX 781094의 순위 이었다. 4) Ethanol 및 hexobarbital유도 수면은 yohimbine에 의해 봉쇄되지 아니하였다. 5) Guanabenz유도 수면시간에 대해서 ${\alpha}_1$-수용체 효현제인 methoxamine 및 Phenylephrine은 영향이 없었으나, ${\alpha}_1$-수용체 결항제인 Prazosin은 증가시켰다. 그러나 corynanthine은 반대로 수면시간을 현저히 감소시켰다. 이상의 결과로 보아 중추 ${\alpha}_2$-수용체의 흥분으로 병아리의 수면이 야기되고, 중추 ${\alpha}_1$-수용체의 역할에 대하여는 명백하지 않으나 ${\alpha}_2$-수용체 효현제 및 길항제의 성질을 규명하는 동물모델로서 부화 I${\sim}$2일의 병아리가 크게 유용할 것으로 시사되는 바이다.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.717-730
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• 1997

$Mg^{2+}$ is the fourth most abundant cation in cellular organisms. Although the biological chemistry and the physiological roles of the magnesium ion were well known, the regulation of intracellular $Mg^{2+}$ in mammalian cells is not fully understood. More recently, however, the mechanism of $Mg^{2+}$ mobilization by hormonal stimulation has been investigated in hearts and in myocytes. In this work we have investigated the regulation mechanism responsible for the $Mg^{2+}$ mobilization induced by ${\alpha}1-adrenoceptor$ stimulation in perfused guinea pig hearts or isolated myocytes. The $Mg^{2+}$ content of the perfusate or the supernatant was measured by atomic absorbance spectrophotometry. The elimination of $Mg^{2+}$ in the medium increased the force of contraction of right ventricular papillary muscles. Phenylephrine also enhanced the force of contraction in the presence of $Mg^{2+}$-free medium. ${\alpha}1-Agonists$ such as phenylephrine were found to induce $Mg^{2+}$ efflux in both perfused hearts or myocytes. This was blocked by prazosin, a ${\alpha}1-adrenoceptor$ antagonist. $Mg^{2+}$ efflux by phenylephrine was amplified by $Na^+$ channel blockers, an increase in extracellular $Ca^{2+}$ or a decrease in extracellular $Na^+$. By contrast, the $Mg^{2+}$ influx was induced by verapamil, nifedipine, ryanodine, lidocaine or tetrodotoxin in perfused hearts, but not in myocytes. $W_7$, a $Ca^{2+}/calmodulin$ antagonist, completely blocked the pheylephrine-, A23187-, veratridine-, $Ca^{2+}-induced$ $Mg^{2+}$ efflux in perfused hearts or isolated myocytes. In addition, $Mg^{2+}$ efflux was induced by $W_7$ in myocytes but not in perfused heart. In conclusion, An increase in $Mg^{2+}$ efflux by ${\alpha}1-adrenoceptor$ stimulation in hearts can be through $IP_3$ and $Ca^{2+}-calmodulin$ dependent mechanism.

• 대한수의학회지
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• 제36권2호
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• pp.327-335
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• 1996

Recently in spite of the interest on the regulation of intracellular $Mg^{2+}$ by neurotransmitters or drugs, the magnesium ion($Mg^{2+}$) regulation by ${\alpha}_1$-adrenoceptor stimulation has not been studied in the heart yet. To elucidate the regulation of ${\alpha}_1$-adrenoceptor stimulation-induced $Mg^{2+}$ release and the effects of ${\alpha}_1$-adrenoceptor stimulation on pathophysiological conditions, in this study we have evaluated the effects of phenylephrine, PMA, $H_7$. staurosporine, verapamil and lidocaine on $Mg^{2+}$ release in perfused guinea pig heart. During preperfusion exogenous $Mg^{2+}$ was added to the medium to give 1.2mM 15min before starting to addition of drugs, and then the infusion of exogenous $Mg^{2+}$ was stopped. $Mg^{2+}$ in the perfusate leaving the heart was measured by atomic absorption spectrophotometry. $Mg^{2+}$ free solution produced an increase in heart rate and phenylephrine elicited $Mg^{2+}$ release from the heart. $Mg^{2+}$ release by phenylephrine was abolished by combined treatment with prazosin. By contrast, cardiac $Mg^{2+}$ uptake induced by a protein kinase C(PKC) activator, PMA was abolished by a selective PKC inhibitor, staurosporine. And the phenylephrine-induced $Mg^{2+}$ release was not affected by the PKC inhibitor, $H_7$. When verapamil or lidocaine was added to perfusing solution, $Mg^{2+}$ release was potentiated by phenylephrine from perfused guinea pig heart. These results suggest that ${\alpha}_1$-adrenoceptor stimulation caused $Mg^{2+}$ release and that PKC is not involved in ${\alpha}_1$-adrenoceptor mediated $Mg^{2+}$ release from perfused guinea pig heart. Under pathophysiological conditions, the $Mg^{2+}$ alteration by ${\alpha}_1$-adrenoceptor stimulation is considerable.

• 대한수의학회지
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• 제35권2호
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• pp.229-236
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• 1995

The effect of ${\alpha}_1$-adrenoceptor(${\alpha}_1$-AR) stimulation on intracellular pH($pH_i$), $Na^+$ activity($a_{Na}{^i}$) and contractility were investigated in isolated papillary muscles of euthyroid or hyperthyroid guinea pig with conventional microelectrode, $Na^+$ or $H^+$-selective microelectrodes, and tension transducer. Stimulation of the ${\alpha}_1$-AR by phenylephrine produced a decrease in $a_{Na}{^i}$ in euthyroid preparations. This decrease in $a_{Na}{^i}$ was abolished in presence of PKC activator, phorbol dibutyrate, and increased contrary to decrease. Phenylephrine also increased $a_{Na}{^i}$ in hyperthyroid ones. However, phenylrephtine produced an increase in $pH_i$ in both euthyroid and hyperthyroid ones. These changes were blocked by prazosin, an antagonist of ${\alpha}_1$-AR. These findings suggest that the changes in $a_{Na}{^i}$ and $pH_i$ are mediated by a stimulation of $Na^+-H^+$ exchange via ${\alpha}_1$-AR stimulation. This study focused on the increase in $a_{Na}{^i}$, $pH_i$ and contractility. The increase in $pH_i$ was blocked by amiloride or EIPA, $Na^+-H^+$ exchange inhibitors. Therefore, the increase in $a_{Na}{^i}$ and $pH_i$ mediated by ${\alpha}_1$-AR appeared to be due to an influx of $Na^+$ and a reduction of $H^+$ through $Na^+-H^+$ exchange. This study also revealed that the increase in $pH_i$ and $a_{Na}{^i}$ might be related to the sustained positive inotropic response. The $a_{Na}{^i}$ increase may contribute to the intracellular $Ca^{2+}$ through the $Na^+-Ca^{2+}$ exchange, and the $pH_i$ increase could cause an increase in the $Ca^{2+}$ sensitivity of myofilaments and may augment the ${\alpha}_1$-AR-mediated positive inotropic response.