• 대한수의학회지
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• 제38권3호
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• pp.508-517
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• 1998

There is evidence that the sympathetic nervous system exerts a control on thyroid function via an adrenergic innervation of thyroid cells. Although it is clear that the inhibitory effects of catecholamines result from an activation of ${\alpha}_1$-adrenoceptors, the mechanisms involved in ${\alpha}_1$-stimulation are not fully understood. The effects of methoxamine and protein kinase C (PKC) activator on the release of thyroxine ($T_4$) from mouse thyroid were studied to clarify the role of PKC in the regulation of $T_4$ release in vitro. The glands were incubated in the medium, samples of the medium were assayed for $T_4$ by EIA kits. Methoxamine inhibited the TSH-stimulated $T_4$ release. This inhibition was reversed by prazosin, an ${\alpha}_1$-adrenergic antagonist. Futhermore, the inhibitory effect of methoxamine on the $T_4$ release stimulated by TSH was prevented by chloroethylclonidine, an ${\alpha}_{1b}$-adrenoceptor antagonist, but not by WB4101, an ${\alpha}_{1a}$-adrenoceptor antagonist. Also methoxamine inhibited the forskolin-, cAMP- or IBMX-stimulated $T_4$ release. These inhibition were reversed by PKC inhibitors, such as staurosporine and $H_7$. PMA, a PKC activator, completely inhibited the TSH-stimulated $T_4$ release, and its inhibition was reversed by staurosporine and $H_7$, but not by chelerythrine. R59022 (a diacylglycerol kinase inhibitor), like methoxamine, also inhibited the TSH-stimulated $T_4$ release, and its inhibition was also reversed by staurosporine. The present study suggests that methoxamine inhibition of $T_4$ release from mouse thyroid can be induced by activation of the ${\alpha}_{1b}$-adrenoceptors and that it is mediated through the ${\alpha}_1$-adrenoceptor-stimulated PKC formation.

• 대한약리학회지
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• 제22권2호
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• pp.115-122
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• 1986

Urethane 마취 가토에서 뇌내 alpha-1및 alpha-2 adrenoceptor의 작용에 미치는 calcium antagonist의 영항을 알아보고자 뇌실내 methoxamine과 clonidine의 혈압및 심박수 변동에 미치는 diltiazem, nifedipine의 영향을 조사한 결과, 1). 뇌실내 methgramine(1mg)은 혈압상승및 심박수 감소를 일으켰고, 뇌실내 clonidine$(30{\mu}g)$은 혈압하강및 심박수 감소를 일으켰다. 2). 뇌실내 diltiazem과 nifedipine은 dose-dependent한 혈압하강을 일으켰으며 심박수 감소를 일으켰다. Diltiazem에 비하여 nifedipine은 혈압하강 효과는 크고 심박수 감소효과는 작았다. 뇌실내 diltiazem$(400{\mu}g)$, nifedipine$(35{\mu}g)$의 혈압하강 작용은 완만하고 지속적이었으나 같은 양의 정맥내 투여효과는 일과성이었다. 3). 뇌실내 diltiazem$(400{\mu}g)$이나 nifedipine$(35,\;350{\mu}g)$ 처리 후에 methoxamine(1mg)의 혈압상승 효과는 영향받지 않았으나 심박수감소 효과는 유의하게 감약되었다. 4). Clonidine의 혈압하강 작용은 뇌실내 diltiazem$(400{\mu}g)$이나 nifedipine$(35,\;350{\mu}g)$ 처리 후에 감약되었으나 정맥 내 diltiazem$(200{\mu}g/kg)$이나 nifedipine$(30{\mu}g/kg)$ 후에는 영향받지 않았다. Clonidine의 심박수 감소작용은 .뇌실내및 정맥내 diltiazem이나 nifedipine 처리후에 감약되었다. 5). 뇌실내 clonidine$(30{\mu}g)$ 처 리후 뇌실내 diltiazem$(400{\mu}g)$과 nifedipine$(350{\mu}g)$의 혈압하강및 심박수 감소효과는 영향 받지 않고 그대로 나타났다. 이상의 결과로 diltiazem과 nifedipine은 가토뇌내에서 methoxamine에 의한 혈압상승의 작용점인 alrfia-1 adrenoceptor의 흥분에는 영향을 미치지 못하나 clonidine의 작용점인 alpha-2 adrenoceptor의 흥분에 의한 혈압하강및 심박수 감소효과는 억제한다고 추론하였다.

• 대한수의학회지
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• 제39권6호
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• pp.1073-1080
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• 1999

Previous studies suggested that the inhibition of thyroxine ($T_4$) release by ${\alpha}_1$-adrenoceptor and muscarinic receptor stimulation results in activated protein kinase C (PKC) from mouse and guinea pig thyroids. In the present study, the effect of carbachol, methoxamine, phorbol myristate acetate (PMA), and R59022 on the release of $T_4$ from the mouse, rat, and guinea pig thyroids was compared to clarify the role of PKC in the regulation of the release of $T_4$. The thyroids were incubated in the medium containing the test agents, samples of the medium were assayed for $T_4$ by EIA kits. Forskolin, an adenylate cyclase activator, chlorophenylthio-cAMP sodium, a membrane permeable analog of cAMP, and isobutyl-methylxanthine, a phosphodiesterase inhibitor, like TSH (thyroid stimulating hormone), enhaced the release of $T_4$ from the mouse, rat, and guinea pig thyroids. Methoxamine, an ${\alpha}_1$-adrenoceptor agonist, inhibited the TSH-stimulated release of $T_4$ in mouse, but not rat and guinea pig thyroids. In contrast, carbachol, a muscarinic receptor agonist, inhibited the release of $T_4$ in guinea pig, but not mouse and rat thyroids. These inhibition were reversed by prazosin, an ${\alpha}_1$-adrenoceptor antagonist or atropine, a muscarinic antagonist or $M_1$- and $M_3$-muscarinic antagonists, in mouse or guinea pig thyroids. In addition, staurosporine, a PKC inhibitor, reversed methoxamine or carbachol inhibition of TSH stimulation. Furthermore, PMA, a PKC activator, and R59022, a diacylglycerol (DAG) kinase inhibitor, inhibited the TSH-stimulated release of $T_4$ in mouse, rat, and guinea pig thyroids. These inhibition were blocked by staurosporine. These findings suggest that the activation of receptor or DAG inhibits TSH-stimulated $T_4$ release through a PKC-dependent mechanism in thyroid gland.

• 한국어병학회지
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• 제9권1호
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• pp.41-51
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• 1996

경골어류의 혈관평활근에 대한 adrenaline성 조절기작을 규명의 일환으로 틸라피아의 배대동맥을 사용하여 Adrenergic agonist의 효과와 그 매개에 관여하는 수용체의 subtype에 대한 연구를 하였으며 그 결과는 다음과 같다. 1. Epinephrine, norepinephrine, phenylephrine, clonidine 및 methoxamine은 tilapia의 배대동맥에 대하여 농도의존적인 혈관수축효과만을 나타내었으며, 효력은 epinephrine, norepinephrine, phenylnephrine, clonidine, methoxamine의 순이었으며, 이들 수축반응은 혈관내피세포의 존재유무에 영향을 받지 않았다. 2. Epinephrine, norepinephrine, phenylephrine 및 clonidine 의 농도의존적인 혈관수축반응곡선은 선택적인 $\alpha_2$-adrenergic 수용체 길항제인 yohimbine의 농도가 증가함에 따라 오른쪽으로 평행이동 되었으며, epinephrine과 norepinephrine은 선택적인 $\alpha_1$-수용체 길항제인 prazosin의 농도가 증가함에 따라 오른쪽으로 평행이동되었다. 3. Epinephrine과 norepinephrine의 혈관수축반응은 calcium제거 생리적 완충용액에서는 각각 약 41%, 51% 소실되었며, calcium 유입차단제인 verapamil에 의해서도 거의 유사한 경향을 보였다. 이상의 실험결과들을 종합하면 Catecholamine류는 수축효과만을 나타내었으며 혈관내피세포 존재유무와는 무관하였다. 이러한 수축작용은 $\alpha_1$- 및 $\alpha_2$-adrenergic receptor가 모두 매개하였으며 voltage dependent $Ca^{2+}$ channel을 통하여 유입된 세포외액의 $Ca^{2+}$과 세포내 $Ca^{2+}$의해 일어난다고 사료된다.

• 대한수의학회지
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• 제38권4호
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• pp.712-719
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• 1998

Thyroid function is mainly regulated through cAMP and phophatidylinositol, and it is well known that TSH-stimulated thyroxine ($T_4$) release is inhibited by catecholamine from mouse thyroids via the ${\alpha}_1$-adrenoceptor stimulation. Previous study has established that the inhibition of $T_4$ release by ${\alpha}_1$-adrenoceptor stimulation results in activated protein kinase C (PKC). The purpose of this study was to determine if ion transport systems are involved in the inhibition of $T_4$ release elicited by ${\alpha}_1$-adrenergic agonist in mouse thyroids. TSH-, IBMX- and cAMP analogue-stimulated $T_4$ release were significantly inhibited by methoxamine, R59022 (diacylglycerol kinase inhibitor), and MDL (adenylate cyclase inhibitor). TSH-stimulated $T_4$ release could be inhibited by Bay K 8644 and cyclopiazoic acid, but not by verapamil and tetrodotoxin. The addition of nifedipine ($Ca^{2+}$ channel blocker), tetrodotoxin and lidocaine ($Na^+$ channel blockers), but not amiloride (EIPA) and ryanodine, completely blocked the inhibitory effects of methoxamine on $T_4$ release. TSH-stimulated $T_4$ release was also inhibited by benzamil ($Na^+-Ca^{2+}$ exchange inhibitor). TSH-, IBMX- and cAMP-stimulated $T_4$ release were inhibited by methoxamine or R59022, these effects were reversed by nifedipine. but not by verapamil. Furthermore, nifedipine reversed the inhibitory effects of benzamil and R59022 on TSH-stimulated $T_4$ release. These data suggest that the observed ${\alpha}_1$-adrenoceptor-mediated inhibition of $T_4$ release in mouse thyroids is the result of an increase in intracellular $Na^+$ or $Ca^{2+}$ effected via activation of fast $Na^+$ or nifedipine-sensitive $Ca^{2+}$ channels, and that $Na^+-Ca^{2+}$ exchange may play an important role in reducing thyroid hormone by increasing intracellular $Ca^{2+}$.

• 한국식품영양과학회지
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• 제14권3호
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• pp.253-258
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• 1985

흰쥐 정관 및 꼬리 동맥의 ${\alpha}_1-$및 ${\alpha}_2-$수용체, 그리고 prostaglandine과 관련해 NA 유리에 미치는 Cd의 영향을 관찰하여 다음과 같은 결과를 얻었다. 1. Cd 중독 흰쥐 정관에서 전기 자극에 대한 반응은 증가하였으며, Freq.50은 대조군보다 현저히 낮아졌으며 꼬리동맥의 반응은 감약되었다. 2. Cd 중독 정관에서 clonidine의 억제반응은 유의하게 감소하였으나 methoxamine 존재하의 전기 자극 반응은 영향을 받지 아니하였다. 3. $PGE_2$에 의한 억제작용은 Cd 중독군에서는 소실되었으나 꼬리 동맥에서 $PGE_2$의 억제효과는 Cd 중독으로 영향을 받지 아니하였다. 4. Cd 중독 꼬리 동맥에서 methoxamine 및 clonidine에 대한 수축반응은 최대 수축고가 현저히 낮아졌으나 $ED_{50}$치는 변화하지 아니하였다. 이상의 결과로 보아 Cd 중독시 정관에서 시냅스 전막 autoreceptor가 억제되어 교감 신경 흥분성이 증가함으로써 전기자극에 대한 반응이 항진되었다고 생각된다.

• 대한약리학회지
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• 제20권2호
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• pp.49-57
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• 1984

The exocrine pancreatic secretion is controlled mainly by gastrointestinal hormones as well as cholinergic nerves. The adrenergic influence on exocrine pancreas is thought not to he important and the evidences supporting this contention are still contradictory. In an effort to elucidate the adrenergic influence on the exocrine pancreas, we have determined the amylase release from pancreatic slices of rats treated with adrenergic drugs. The albino rats of either sex, weighing $60{\sim}80\;g$, were decapitated and the uncinate pancreata were isolated and incubated in screw top vials containing 2 ml krebs-Ringer bicarbonate buffer solution gassed with 95% $O_2$ and 5% $CO_2$. These vials were shaken continuously in a waterbath maintained at $37^{circ}C$, and enzyme release was stimulated with acetylcholine$(10^{-5}M)$. For chronic treatment methoxamine$(an\;{\alpha}-adrenergic\;agonist,\;5\;mg/kg)$, isoproterenol (a\;{\beta}-adrenergic\;agonist,\;10\;mg/kg) and reserpine (0.5 mg/kg) along with cholecystokinin octapeptide$(CCK-op,\;2{\mu}g/kg)$ were given i.p. in rats daily for 3, 5, 7, 9 or 12 days. For acute experiment these drugs were added directly to the incubation medium in a concentration of $10^{-5}M$ except CCK-OP $(10^{-9}M)$. The results are summarized as follows. 1) The addition of methoxamine, isoproterenol or reserpine to the incubation medium containing pancreatic slices augmented the release of amylase induced by acetylcholine and among them the effect of isoproterenol was most prominent. 2) Chronic treatment of methoxamine or reserpine caused enhancement of acetylcholine response in amylase release from pancreatic slice throughout the experimental period, but the amylase release was less than that of control by 12 days isoproterenol treatment. 3) In the pancreatic slices obtained from 12 days treatment of CCK-OP, the amylae release responding to acetylcholine was enhanced. By these finding it is suggested that methoxamine, isoproterenol and reserpine had marked influence on the exocrine pancreatic functions in rats and that these effects are due to their inherent actions rather than sympathetic nerve or adrenergic receptor function.

• Journal of Chest Surgery
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• 제23권6호
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• pp.1107-1117
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• 1990

The regulatory role of the post \ulcorner1-and \ulcorner2-adrenoceptors on cardiac function, particularly in coronary flow rate, was investigated in the isolated rat heart treated with 10-6 M propranolol. When introduced into the left atrium of the heart, phenylephrine[10-7-10-2 M] decreased coronary flow rate and increased mean coronary resistance in a dose related fashion, but did not affect heart rate. Methoxamine also elicited the increment of coronary resistance and the decrement of coronary flow rate, though the effects of methoxamine were weaker than those by phenylephrine. The effect of phenylephrine was inhibited by 1\ulcornerM prazosin and shifting the dose-response curve to the right. The effects of clonidine, a selective \ulcorner2-adrenoceptor agonist, were studied in the heart taken from reserpinized rats. Clonidine increased coronary resistance, decreased heart rate and coronary flow rate with a dose-dependent manner. These effects were abolished by 10-6 M yohimbine, a selective \ulcorner2-antagonist, and were not affected by 10-6M prazosin. Clonidine also decreased coronary flow and increased mean coronary resistance in electric paced heart. These effects were inhibited by rawoulscine, a selective ca-antagonist. These results indicate that the stimulation of both post \ulcorner1-and \ulcorner2-adrenoceptor causes coronary vasoconstiction. And it is inferred that this model of sympathomimetics-induced coronary vasospasm may provide a useful tool for investigating spasmolytic agents which are of benefit in the treatment of variant angina.

• 대한약리학회지
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• 제5권1호
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• pp.35-38
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• 1969

1.On isolated atrial preparation of frog, effects of sympathomimetic amines were investigated. 2. Isoproterenol, epinephrine, norepinephrine, and phenylephrine produced positive chronotropic and inotropic effects. The relative potencies for the effects of these agents were: isoproterenol > epinephrine> norepinephrine> phenylephrine. Methoxamine had no effects or depressed the atria. 3. Pronethalol antagonized the positive effects of these adrenergic agents competitively. 4. Regitine did not affect the effects of these agents. 5. These data indicate that the adrenergic agents activate the atrial tissue of the frog via stimulation of adrenergic beta-receptor.

• 대한약리학회지
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• 제21권1호
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• pp.27-33
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• 1985

전기자극에 의한 적출 정관의 수축 또는 뇌척수제거 흰쥐의 심박동수 증가가 카드뮴 장기투여 (매격일 $10{\mu}$ mols, 1회씩 2주간 복강내 주사)로 인하여 대조군에 비하여 현저히 항진되었다. 이러한 전기자극에 의한 반응은 ${\alpha}_2$-효현제인 clonidine에 의하여 억제 되었고, 이 억제는 ${\alpha}_2$-길항제인 yohimbine 투여로 봉쇄되었다. 나아가 methoxamine에 의한 확장 혈압의 증가는 카드뮴 투여에 의하여 영향을 받지 아니하였으나 clonidine에 의한 증가는 카드뮴 투여에 의하여 억제되었다. 이러한 결과로 보아 카드뮴 장기 노출에 의하여 시납스 전 및 후 ${\alpha}2-adrenoceptors$가 우선적으로 억제되었다고 시사되는 바이다.