• The Korean Journal of Physiology and Pharmacology
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• 제25권6호
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• pp.525-532
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• 2021

We have investigated the relative roles of α₁-adrenoceptors and purinoceptors in contractions to low and high frequency stimulation of the mouse vas deferens, in terms of the time course of responses. In separate experiments, isometric contractile responses were obtained to 10 pulses at 1 Hz and 40 pulses at 10 Hz. Responses to 1 Hz stimulation consisted of a series of discrete peaks. The α_1A-adrenoceptor antagonist RS100329 (10^-9M-10^-7M) significantly reduced the response to the first pulse, the α_1D-adrenoceptor antagonist BMY7378 (10^-7M-10^-6M) significantly reduced the response to the first two pulses, and the non-selective α₁-adrenoceptor antagonist prazosin (10^-8M) reduced the response to the first 4 pulses at 1 Hz. Responses to 10 Hz stimulation consisted of an early peak response and a maintained plateau response. RS100329 significantly reduced the peak response but did not significantly affect the plateau response. Prazosin, significantly reduced both the peak and plateau responses. The α_1A-adrenoceptor antagonist RS17053 in high concentrations reduced mainly the plateau response leaving a clear early peak response. The plateau response of contraction was almost abolished by the purinoceptor antagonist suramin. These results suggest that there is a relatively minor early α_1D-adrenoceptor and a larger early α_1A-adrenoceptor component to stimulationevoked contractions of mouse vas deferens, but the major α₁-adrenoceptor component is revealed by prazosin to be α_1B-adrenoceptor mediated. α_1B-Adrenoceptor activation probably facilitates contractions mediated by other α₁-adrenoceptors and by purinoceptors. These results suggest that combined non-selective α₁-adrenoceptor blockade, particularly α_1B-adrenoceptor blockade, in addition to P2X1-purinoceptor blockade is useful in reducing male fertility.

• 한국동물위생학회지
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• 제17권3호
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• pp.255-263
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• 1994

To elucidate the action of the adrenergic nerve on the isolated uterine smooth muscle of the pig, effects of electrical transmural nerve stimulation and norepinephrine were investigated on the pretreatment of phentolamine ； non-selective ${\alpha}$-adrenoceptor blocker, propranolol ; ${\beta}$-adrenoceptor blocker and the yohimbine；${\alpha}_2$-selective adrenoceptor blocker from physiograph. 1. The relaxation response induced by norepinephrine was the concentration of $10^{-6}$ M at first and maximum response was concentration of $10^{-4}$M. 2. The relaxation response induced by norepinephrine was not effected by the pretreatment with non-selective $\alpha$-adrenoceptor blocker, phentolanune ($10^{-6}$ M) but was completely blocked by the pretreatment with ${\beta}$-adrenoceptor blocker, propranolol($10^{-6}$ M). 3. The contractile response induced by electrical transmural nerve stimulation(20V, 10Hz, 0.5msec, 20sec ) was inhibited by the pretreatment with non-selective ${\alpha}$-adrenoceptor blocker, phentolamine($10^{-6}$ M) but was not inhibited and rather increased by the pretreatment ${\beta}$-adrenoceptor blocker, propranolol($10^{-6}$ M), and was not approximately effected by the pretreatment with ${\alpha}_2$-adrenoceptor blocker, yohimbine($10^{-6}$ M). These finding suggest that it was excitatory action by ${\alpha}_1$-adrenergic nerve and inhibitory action by ${\alpha}_2$-adrenergic, ${\beta}$-adrenergic nerve on uterine smooth muscle of the pig.

• 약학회지
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• 제35권5호
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• pp.416-426
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• 1991

The effects of an irreversible or a reversible $\alpha_1$-adrenoceptor antagonist (dibenamine or prazosin) on $\alpha_1$-adrenoceptor-mediated vasoconstrictions were studied in the endothelium-denuded rat aorta. In these experiments, the mobilization of intracelluier calcium and translocation of extracellular calcium were also studied. To exclude the modulation of endothelium releasing EDRF and EDCF, the endothelium was removed in all rat aortas. Contraction induced by phenylephrine (a full $\alpha_1$-adrenoceptor agonist) was separated into a fast phasic component of the response due to the release of intracellular calcium and a slow tonic one due to the influx of extracellular calcium. Pretreatments with increasing doses of reversible $\alpha_1$-adrenoceptor antagonist prazosin, as well as irreversible $\alpha_1$-adrenoceptor antagonist dibenamine, inhibited the phasic component of phenylephrine-induced contraction more effectively than the tonic one. Pretreatment of dibenamine (0.2 $\mu{M}$) or prazosin (10 nM) to the rat aorta abolished phasic response but remained tonic one about 41% and 51%, respectively. These results suggest that as the efficiency of phenylephrine was progressively reduced by pretreatments with increasing doses of an irreversible or a reversible $\alpha_1$-adrenoceptor antagonist (dibenamine or prazosin), the contraction induced by phenylephrine became progressively more dependent on the influx of extracellular calcium.

• 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.

• 한국임상약학회지
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• 제33권2호
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• pp.86-96
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• 2023

Background: Using KIDS-KAERS database (KIDS-KD) from 2016 to 2020, the aim is to investigate signals of adverse events of alpha-adrenoceptor antagonists and to present adverse events that are not included in the precautions for use when marketing approval. Methods: This study was conducted by disproportionality analysis. Data mining analysis was performed to detect signals of alpha-adrenoceptor antagonists, such as terazosin, doxazosin, alfuzosin, silodosin, and tamsulosin. The signal was defined by three criteria as proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). Detected signals were compared with product labeling and the European Medicines Agency-Important Medical Events list. Results: Out of the total number of 408,077 reports for adverse events, 6,750 cases were reported as adverse events of alpha-adrenoceptor antagonists. Dizziness, mouth dryness, hypotension postural, and oedema peripheral are identified as common adverse events of five alpha-adrenoceptor antagonists and are typically listed on drug labels. However, new signals were detected for pneumonia, chronic obstructive airway disease, eye diseases such as glaucoma and cataracts, fracture, and ileus of tamsulosin that were not previously listed on the drug labels in Korea. Conclusions: This study identified signals related to adverse drug reactions of alpha-adrenoceptor antagonists and presented serious adverse events, suggesting new adverse reactions to be aware of when using alpha-adrenoceptor antagonists.

• 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.

• The Korean Journal of Physiology
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• 제27권1호
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• pp.27-35
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• 1993

Effects of the endothelium on the contractile responses to norepinephrine (NE) were investigated in isolated helical strips of the proximal and distal coronaries artery of pigs. The helical strips were immersed in Tris-buffered Tyrode's solution equilibrated with 100% $O_2$ at $35^{\circ}C$ and its isometric tension was measured. NE relaxed the strips precontracted with acetylcholine from both the proximal and distal coronary artery. NE-induced relaxation, which might be induced mainly by $\beta$-adrenoceptor function was dominant in the distal coronary arteries. NE-induced relaxation was converted to a contraction after $\beta$-adrenoceptor blockade with propranolol $(3{\times}10^{-6}M)$. ${\alpha}$-adrenoceptor-mediated contraction by NE was greater in the proximal coronary artery than the distal coronary artery. Quantitatively, ${\alpha}_1$-adrenoceptor mediated contraction by NE was greater than ${\alpha}_2$-adrenoceptor mediated contraction by NE in both arteries. NE-induced relaxation was decreased by rubbing of endothelium in both arteries. ${\alpha}_1-and\;{\alpha}_2$-adrenoceptor mediated contraction by NE were potentiated by rubbing of endothelium in both arteries. Pretreatment with methylene blue, an inhibitor of soluble guanylate cyclase, increased ${\alpha}_1-\;and\;{\alpha}_2$-adrenoceptor mediated contraction by NE in both arteries with endothelium. From the above results, we suggest that the effect of activation of $\alpha$-adrenoceptors by NE may be modulated by endothelium in the proximal and distal coronary arteries of pigs. This effect may be mediated via endothelium derived relaxing factor.

• 대한약리학회지
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• 제22권1호
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• pp.45-50
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• 1986

후신경구절제(OB) 흰쥐에 있어서 muricide의 발생은 중추성 ${\alpha}$-adrenoceptors의 기능항진과 밀접한 관계가 있다는 가설하에 다음 실험을 행하였다. Muricide를 일으키는 OB 흰쥐의 전뇌내 noradrenaline(NA)의 전환율은 대조군에 비하여 현저히 낮았으나 $_{{\alpha}_2}$-adrenoceptor 길항약물인 yohimbine이나 idazoxan 투여시 NA 전환은 muricide의 억제와 함께 현저히 증가되었다. OB흰쥐의 전뇌 피질막의 $[^3H]$ yohimbine에 대한 최대결합능(Bmax)은 대조군에 비하여 현저히 높았다. ${\alpha}$-Adrenoceptor 효능약물 및 길항약물에 대한 친화도는 아무런 변동이 없었다. 이상의 결과로 보아 OB흰쥐에서 야기되는 muricide는 중추성 ${{\alpha}_2}$-adrenoceptor의 기능 항진과 밀접한 관련이 있다고 사료되는 바이다.

• 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.

• Bulletin of the Korean Chemical Society
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• 제25권12호
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• pp.1784-1790
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• 2004

A series of 2-(3-chlorophenyl)-2-hydroxyethylamine derivatives containing a tetrahydrocarbazole linker were prepared and evaluated for their ${\beta}_3$-adrenoceptor agonistic activity. Several compounds showed potency comparable to CL-316243.