• Title/Summary/Keyword: ${\alpha}$-adrenoceptors

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Postsynaptic $\alpha_1$-, $\alpha_2$-Adrenoceptors in Rat Isolated Aorta (적출한 흰쥐 대동맥에 있어서 postsynaptic $\alpha_1$-, $\alpha_2$- 아드레날린 수용체에 관한 연구)

  • 임광진;조윤성;고광호;김미영
    • YAKHAK HOEJI
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    • v.30 no.3
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    • pp.157-162
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    • 1986
  • $\alpha$-Adrenoceptor subtypes in the isolated rat aortic strips were examined by using agonists and antagonists which have varying selectivity for $\alpha_1$- and $\alpha_2$- adrenoceptors. Norepinephrine and phenylephrine produced a similar magnitude of maximum contractions. $pA_2$ values for prazosin and yohimbine were not significantly different using norepinephrine or phenylephrine as the agonist, suggesting a single population of alpha-adrenoceptor. Contractile responses produced by alpha-agonists were antagonized more effectively by prazosin (approximately 1000 fold) than by yohimbine.

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Involvement of α1B-adrenoceptors and Rho kinase in contractions of rat aorta and mouse spleen

  • Hadeel A. Alsufyani;James R. Docherty
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.4
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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 α1A-adrenoceptor antagonist RS100329 had low potency in rat aorta. The α1D-adrenoceptor antagonist BMY7378 antagonized contractions in rat aorta in a biphasic manner: low concentrations blocking α1D-adrenoceptors and high concentrations blocking α1B-adrenoceptors. The Rho kinase inhibitor fasudil (10 µM) significantly reduced aortic contractions in terms of maximum response, suggesting inhibition of α1B-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 α1B- and α1D-adrenoceptors, and the late component involving α1B- and α1A-adrenoceptors. This suggests that fasudil inhibits α1B-adrenoceptor mediated responses. It is concluded that α1D- and α1B-adrenoceptors interact in rat aorta and α1D-, α1A- and α1B-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 α1B-adrenoceptor.

Study on Alpha-Adrenoceptors of the Isolated Atrium in Cold Blood Animals (I) -Experiments with clonidine, oxymetazoline and phenylephrine in frog atria- (척출 냉혈동물 심방의 Alpha-Adrenoceptors에 관한 연구(I) -개구리 심방의 clonidine, oxymetazoline 및 phenylephrine에 대한 반응-)

  • Choi, Soo-Hyung;Park, Haeng-Soon;Shin, Dong-Ho
    • YAKHAK HOEJI
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    • v.32 no.2
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    • pp.129-136
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    • 1988
  • Effects of the selective alpha-adrenoceptor agonists, clonidine, oxymetazoline and phenylephrine, on heart rate and contractile force were investigated in the isolated frog atria and it was attempted to examine the influence of adrenoceptor antagonist upon those. Clonidine produced dose-dependent negative chronotropic and positive inotropic effects. The negative chronotropic effect was significantly attenuated in the presence of prazosin and yohimbine but not propranolol. The positive inotropic effect was significantly attenuated by prazosin, yohimbine and propranolol. Oxymetazoline produced dose-dependent negative chronotropic and inotropic effects. The negative chronotropic effect was significantly attenuated in the presence of prazosin, which was partially augmented by yohimbine but was not affected by propranolol. The negative inotropic effect was not affected by propranolol but it was partially augmented by yohimbine and was partially attenuated by prazosin. Phenylephrine produced dose-dependent positive chronotropic and inotropic effects. The positive chronotropic and inotropic effect were significantly attenuated in the presence of propranolol but were not affected by prazosin and yohimbine. These results suggest that the negative chronotropic effect by clonidine and oxymetazoline is mediated by alpha-adrenoceptors, the positive chronotropic and inotropic effects by phenylephrine are mediated by beta-adrenoceptors, and alpha-adrenoceptors mediated the inhibitory chronotropic responses exists in the isolated frog atria.

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Pharmacological Characterization of (10bS)-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline Oxalate (YSL-3S) as a New ${\alpha}_2$-Adrenoceptor Antagonist

  • Chung, Sung-Hyun;Yook, Ju-Won;Min, Byung-Jun;Lee, Jae-Yeol;Lee, Yong-Sup;Jin, Chang-Bae
    • Archives of Pharmacal Research
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    • v.23 no.4
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    • pp.353-359
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    • 2000
  • ${\alpha}_2$-Adrenoceptor antagonists, which can enhance synaptic norepinephrine levels by blocking feedback inhibition processes, are potentially useful in the treatment of disease states such. as depression, memory impairment, impotence and sexual dysfunction. (10bS)-1,2,3,5,6,10b-Hexahydropyrrolo[2,1-a]isoquinoline oxalate (YSL-3S) was evaluated in several in vitro biological tests to establish its pharmacological profile of activities as an ${\alpha}_2$-adrenoceptor antagonist. Saturation binding assay revealed that$^{3}[H]$rauwolscine bound to the $\alpha$$_2$-adrenoceptors with a Kd value of 6.3$\pm$0.5 nM and a Bmax value of 25l$\pm$39 fmol/mg protein in rat cortical synaptic membranes. Competitive binding assay showed that YSL-3S inhibited the binding of$^3[H]$rauwolscine (1 nM) in a concentration-dependent manner with a Ki value of 98.2$\pm$12.1 nM while it did not inhibit the binding of [$^3$H]cytisine (1.25 nM) to neuronal nicotinic cholinergic receptors. The Ki values of yohimbine, clonidine and norepinephrine for $^3[H]$rauwolscine binding were 15.8$\pm$1.0, 40.1$\pm$5.9 and 40.0$\pm$11.5 nM, respectively. In addition, the binding affinity of YSL-3S for ${\alpha}_2$-adrenoceptors was higher than that of its antipode and the racemic mixture. The functional activity of YSL-3S at the presynaptic ${\alpha}_2$-adrenoceptors was assessed using the prostatic portion of the rat vas deferens. Clonidine inhibited field-stimulated contractions of the vas deference in a dose-dependent manner. The presence of YSL-3S or yohimbine caused a parallel, rightward the dose-response curve of clonidine in a dose-dependent manner, indicating an antagonistic action at the presynaptic ${\alpha}_2$-adrenoceptors. The $pA_2$values of yohimbine and YSL-3S were 7.66$\pm$0.13 and 6.64$\pm$0.18, respectively. The results indicate that YSL-3S acts as a competitive antagonist at presynaptic ${\alpha}_2$ -adrenoceptors with a potency approximately ten times lower than yohimbine, but is devoid of binding affinity for neuronal nicotinic cholinergic receptors.

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Effects of Clonidine on the Negative Chronotropic Response Induced by Vagal Stimulation in the Rat

  • Hong, Sung-Cheul;Huh, Kyung-Hye;Chung, Joon-Ki;Park, Mi-Sun
    • Archives of Pharmacal Research
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    • v.11 no.1
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    • pp.65-73
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    • 1988
  • The effects of clonidine on the negative chronotropic response induced by stimulation of vagus nerve were studied in the presence of propranolol in reserpinized and anesthetized rats. When the heart rate was decreased by stimulation of the vagus nerve, clonidine significantly inhibited vagally induced heart rate decrease (negative chronotropic response) in dose dependent manner. This inhibitory effect of clonidine was virtually abolished by phentolamine, ${\alpha}_1-\;and\;{\alpha}_2-adrenoceptor$ antagonist, and partially antagonized by prazosin, ${\alpha}_1-adrenoceptor$ antagonist. On the other hand, when the heart rate was decreased by the infusion of bethanechol, a muscarinic parasympathetic stimulant, clonidine had no effect on the bethanechol-induced heart rate decrease. These results suggest that clonidine inhibits vagally induced negative chronotropic response by activation of presynaptic ${\alpha}-adrenoceptors$ located on the parasympathetic cholinergic nerve terminal in the heart and this effect of clonidine is more related to ${\alpha}_2-adrenoceptors$ than ${\alpha}_1-adrenoceptors$.

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Inhibitory Effects of B-HT 920 on Gastric Acid Secretion Induced by Vagal Stimulation in Rat

  • Hong, Sung-Cheul;Park, Mi-Sun;Chung, Joon-Ki;Kang, Maeng-Hee;Choi, Su-Kyung;Kim, Myung-Woo
    • Archives of Pharmacal Research
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    • v.12 no.4
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    • pp.243-248
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    • 1989
  • Effects of B-HT 920 on the vagally stimulated gastric acid secretion were studied in anesthetized and gastric fistula rats. When the gastric acid secretion was increased by stimulation of the vagus nerve, B-HT 920 was partially attenuated by prazosin, $\alpha_1-$adrenoceptor antagonist and virtually abolished by yohimbine, $\alpha_2-$adrenoceptor antagonist. On the other hand, when the gastric acid secretion was increased by the infusion of bethanechol, a muscarinic parasympathetic stimulant, B-HT 920 had no effect on the bethanechol-induced gastric acid secretion. These results suggest that B-HT 920 inhibits vagally induced gastric acid secretion by activation of presynaptic $\alpha-$adrenoceptors located on the vagally stimulated pathways in the gastric wall and this effect of B-HT 920 is more related to $\alpha_2-$adrenoceptors than $\alpha_1-$adrenoceptors.

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Effects of ${\alpha}_1-Adrenergic$ Stimulation on Contractility and Intracellular $Na^+$ Activity of Guinea Pig Ventricular Muscles (기니픽 심근의 수축력과 세포내 $Na^+$ 활성도에 미치는 ${\alpha}_1-Adrenergic$ 수용체 자극효과)

  • Kim, Jin-Sang;Kang, Hyung-Sub;Chae, Soo-Wan;Lee, Chin-Ok
    • The Korean Journal of Pharmacology
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    • v.32 no.2
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    • pp.189-199
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    • 1996
  • Myocardial ${\alpha}_1-adrenoceptors$ have been shown to mediate a biphaslc inotropic response that was characterized by a transient decline followed by a sustained increasing phase in guinea pig ventricular muscle. Recently one group reported that an ${\alpha}_1-adrenoceptors-induced$ intracellular $Na^+$ decrease is linked to fast $Na^+$ channel inhibition and another group reported that it is linked to $Na^+$-$K^+$ pump activation by ${\alpha}_{1b}-adrenoceptors$. But until now, its mechanism is not clear. Therefore, to see whether the $Na^+$channel or $Na^+-K^+$ pump is related to a decrease in intracellular $Na^+$ activity and/or the negative inotropic response, and which ${\alpha}_1-adrenoceptor$ subtype was involved in the decrease in intracellular $Na^+$activity by phenylephrine, we used conventional and sodium selective microelectrodes, and tension transducer to determine the effects of ${\alpha}_1-adrenergic$ stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force in guinea pig ventricular muscles. $10^{-5}$ M Phenylephrine produced a slight hyperpolarization of the diastolic membrane potential, a decrease or increase in $a_N^i_a$, and a biphasic inotropic response. The negative inotropic response accompanied by a decrease in intracellular $Na^+$activity, whereas in muscles showing a remarkable positive inotropic response without initial negative inotropic effect was accompanied by an increase in intracellular $Na^+$ activity. The decrease in intracellular $Na^+$ activity was apparently inhibited by WB4101, an antagonist of the ${\alpha}_{1a}-adrenoceptors$. The decrease in intracellular $Na^+$ activity caused by phenylephrine was not abolished or reduced by a block of the fast $Na^+$ channels. $V_{max}$ also was not affected by phenylephrine. Phenylephrine produced an increase in intracellular $Na^+$ activity in the presence of a high concentration of extracellular $Ca^{2+}$ (in quiescent muscle) or phorbol dibutyrate, a protein kinase C activator(in beating muscle). These suggest that the ${\alpha}_{1a}-adrenoceptors-mediated$ decrease in intracellular $Na^+$ activity may be related to the protein kinase C.

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Chronic Cadmium Administration Preferentially Affects the Responsiveness Mediated by Pre- and Post-synatic ${\alpha}_2$-Adrenoceptors (카드미늄의 만성적 투여가 신경접합 전.후 ${\alpha}_2$-아드레날인 수용체에 의한 반응에 미치는 영향)

  • Hong, Ki-Whan;Rhim, Byung-Yong;Sohn, Uy-Dong
    • The Korean Journal of Pharmacology
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    • v.21 no.1
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    • pp.27-33
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    • 1985
  • Either the contraction of isolated was deferens or the increase of heart rate in the pithed rats induced by electrical stimulation was significantly augmented by cadmium administration (10 ${\mu}mols$ of cadmium acetate every other day for 2 weeks i.p.). These stimulation-induced responses were diminished by ${\alpha}_2$-adrenoceptor agonist, clonidine, and the inhibition was antagonized by yohimbine. Furthermore, the increase in diastolic blood pressure by clonidine was also significantly reduced after cadmium administration, whereas that by methoxamine was not influenced with this dose range of cadmium. With these results it may be postulated that the long-term cadmium exposure may preferentially affect the responsiveness of the presynaptic as well as the postsynaptic ${\alpha}_2$-adrenoceptors.

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Studies on Adrenoceptors Involved in Regulation of Sodium Transport in Frog Skin (개구리 피부에 있어서 Na 수송을 조절하는 Adrenoceptors에 관한 연구)

  • Choi Bong-Kyu;Kim Kyung-Keun;Kim Heung-Kyu;Kook Young-Johng
    • The Korean Journal of Pharmacology
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    • v.22 no.1 s.38
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    • pp.24-33
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    • 1986
  • To ascertain the existence of various adrenoceptors involved in active transport of sodium in the frog skin and to delineate their physiological roles, the influence of various adrenergic agonists and antagonists on the potential difference (PD), short-circuit current (SCC) and total skin conductance (TSC) of the isolated frog skin of Rana nigromaculata were investigated. PD and SCC were determined with Ussing's technique. Drugs were administered to the serosal side of the skin. Experimental results were summarized as follows: 1. The responses to norepinephrine (NE, $6{\times}10^{-8}-6{\times}10^{-5})M$), phenylephrine (PE, $5{\times}10^{-6}-5{\times}10^{-4}M$) and epinephrine (Epi, $5.5{\times}10^{-7}-5.5{\times}10^{-5}M$) were characterized by marked elevation of PD & SCC in dose-related fashion, but the maximal effect attained by Epi was less than those of NE and PE. 2. These increments of PD & SCC were significantly inhibited by prazosin $(2{\times}10^{-6}M)$, a speciflc ${\alpha}_1$-adrenoceptor blocker. The stimulatory effect on PD & SCC were completely abolished by phenoxybenzamine (PBZ, $3.3{\times}10^{-5}M$), an irreversible ${\alpha}$-adrenoceptor blocking agent. Furthermore, with a larger doses of Epi produced marked decline of PD & SCC after the PBZ pretreatment. 3. Isoproterenol (ISP), a ${\beta}$-adrenoceptor agonist, in concentrations ranging from $5{\times}10^{-7}$ to $5{\times}10^{-6}M$ produced dose-related decrease in PD & SCC, which could be abolished by pretreatment with propranolol $(4{\times}10^{-6}M)$, a specific ${\beta}$-adrenoceptor blocker. It was further noted that the effects of Epi on PD & SCC were markedly potentiated by Propranolol pretreatment. 4. Clonidine as well as guanabenz produced increases in PD & SCC and these effects were inhibited more specifically by prazosin pretreatment than by yohimbine. These results indicated that there exist in the frog skin two distinctive types of adrenoceptors, ${\alpha}$ and ${\beta}$, which roughly corresponds to those in mammals, and that the ${\alpha}$ type of adrenoceptors mediate the stimulation of PD & SCC, whereas ${\beta}$-adrenoceptors mediate the inhibition. However, based on evidence at hand, no conclusion could be drawn on the subtype of ${\alpha}$-adrenoceptors which is involved in the stimulation of sodium transport in the frog skin.

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Antagonism of xylazine-induced hypotensive effect by yohimbine in rabbits (가토(家兎)에서 xylazine의 혈압하강(血壓下降) 효과(效果)에 대한 yohimbine의 길항작용(拮抗作用))

  • Shin, Dong-ho
    • Korean Journal of Veterinary Research
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    • v.30 no.3
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    • pp.277-281
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    • 1990
  • Xylazine is commonly used for anesthesia in veterinary medicine and various adverse effects are developed. To examine if the severe hypotensive response associated with xylazine-induced anesthesia might be resulted from the stimulation of presynaptic alpha-2 adrenoceptors or the increase of vagal tone, effects of yohimbine, atropine and atropine with vagotomy on xylazine-induced severe and long-lasting hypotensive responses were investigated in rabbits. The results were summarized as follows: 1) Intravenously injected xylazine(1mg/kg)-induced hypotensive responses were inhibited by yohimbine(p<0.001). 2) Intravenously injected xylazine(1mg/kg)-induced hypotensive responses were not changed by atropine. 3) Intravenously administered xylazine(1mg/kg)-induced hypotensive responses are not changed by atropine with vagotomy. These results indicate that xylazine is thought to cause severe hypotensive response during anesthesia primarily by stimulating presynaptic alpha-2 adrenoceptors and other receptors or mechanisms may participate in the hgpotensive response of xylazine.

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