• Archives of Pharmacal Research
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• 제12권4호
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• pp.282-288
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• 1989

This study was investigated the effects of imipramine (IMI) and electroconvulsive shock (ECS), which are used as antidepressant therapy, on the central $\beta_1$or $\beta_2$ adrenergic receptor in anesthetized rats. The resting blood pressure and heart rate decreased in reserpinized group (5 mg/kg i. p., 24 hr before), but not in order 4 groups i. e. acute IMI (20 mg/kg i. p.. 3-5 hr before), chronic IMI (Same dose, twice a day for 14 days), siggle ECS (sinusoidal 20 Hz, 120 V for 2 sec) and repeated ECS (same condition, daily for 12 days). The increase of heart rate and hypotension evoked by 1 or 3 $\mu$g intracerebroventricular (i. c. v.) administration of (+) dobutamine, $\beta_2$-agonist, 1 or 3 $\mu$g i. c. v. was significantly attenuated in repeated ECS or reserpine treatment. And, the diminuation of pulse pressure of salbutamol also reduced by repeated ECS. These results suggest that IMI or ECS result in attenuation on tachycardia by (+) dobutamine or on hypotension by salbutamol, presumably by which the central $\beta_1$ or $\beta_2$receptor sensitivity may be suppressed, repectively.

• Biomolecules & Therapeutics
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• 제8권4호
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• pp.338-348
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• 2000

The present study was attempted to determine the effect of 5'-(N'-ethylcarboxamido) adenosine (NECA), which is an potent $A_2$-adenosine receptor agonist, on catecholamine (CA) secretion evoked by cholinergic stimulation, membrane depolarization and calcium mobilization from the isolated perfused rat adrenal gland. NECA (20 nM) perfused into the adrenal vein for 60 min produced a time-related inhibition in CA secretion evoked by ACh (5.32x10$^{-3}$ M), high $K^{+}$(5.6x10$^{-2}$ M), DMPP (10$^{-4}$ M for 2 min), McN-A-343 (10$^{-4}$ M for 2 min), cyclopiazonic acid (10$^{-5}$ M for 4 min) and Bay-K-8644 (10$^{-5}$ M for 4 min). Also, in the presence of $\beta$,${\gamma}$-methylene adenosine-5'-triphosphate (MATP), which is also known to be a selective $P_{2x}$-purinergic receptor agonist, showed a similar inhibition elf CA release evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid. However, in adrenal glands preloaded with 20$\mu$M NECA for 20 min under the presence of 20$\mu$M 3-isobutyl-1-methyl-xanthine (IBMX), an adenosine receptors antagonist, CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were much recovered in comparison to the case of NECA-treatment only. Taken together, these results indicate that NECA causes the marked inhibition of CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization. This inhibitory effect may be mediated by inhibiting influx of extracellular calcium and release in intracellular calcium in the rat adrenomedullary chromaffin cells through the adenosine receptor stimulation. Therefore, it is suggested that the inhibitory mechanism of adenosine receptor stimulation may play a modulatory role in regulating CA secretion.n.n.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.43-45
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• 2013

Background: The aim of this epidemiological study was to establish the laterality of breast cancer (BC) and its association with size, receptor status of the primary tumor and bone metastasis (BM) in a local population. Materials and Methods: This retrospective study included cases of BC from Jan-2009 to Dec-2011 who were referred for metastatic work up or follow up survey with Technetium-99m MDP bone scan (BS) to the Nuclear Medicine Department of Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN). A total of 384 patients out of 521 were included and all reviewed for age, primary tumor size (PTS), laterality, receptor status like estrogen receptor (ER) progesterone receptor (PR) and Her-2-Neu receptor, presence or absence of BM with sites of involvement and time interval between diagnosis of BC and appearance of BM. Results: The left to right sided BC proportion was significantly higher than unity (59%:41%; p<0.001). The right sided BC was observed in younger age group (46:52 years; p<0.0001) and with a smaller PTS than the left sided (3.43:4.15 cm; p<0.0001). The patients with BM had relatively higher negative receptor status with a significant predominance of right sided BC. The overall incidence of BM on BS was 28% and relatively higher in right than left breast (33%:24% p=0.068). The average number of BM sites was also significantly greater for the right side (6:4, P<0.0001). The % cumulative risk of BM in right breast was noted at significantly smaller PTS than left side with log rank value of 5.579; p<0.05. The Kaplan Meier survival plot for event free survival of BM in left sided BC was significantly higher than for the right side (log rank value=4.155, p<0.05), with an earlier appearance of BM in right BC. Conclusions: 1) A left sided predominance of BC was seen in local population; 2) right sided BC had a more aggressive behavior with extensive and earlier appearance of BM at relatively younger age, smaller PTS and receptor (s) negativity.

• 식물조직배양학회지
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• 제27권5호
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• pp.375-377
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• 2000

It is now generally accepted that a phosphoinositide cycle is involved in the transduction of a variety of signals in plant cells. In animal cells, the hydrolysis of phosphatidyl-4,5-bisphosphate catalysed by phosphatidylinositol - specific phospholipase C yields to D-myo-inositol - 1,4,5-trisphosphate and diacylglycerol, which are well known second messengers. The binding of InsP$_3$to a receptor located on the endoplasmic reticulum triggers a calcium release from the endoplasmic reticulum. We have detected and partially characterised key components of phosphoinositide signaling. First, tobacco microsomal fraction and plasma membrane PI-PLC. Consecutively, using a radioligand binding assay we have identified a $Ca^{2+}$ -dependent high affinity InsP$_3$binding site in microsomal membrane fraction vesicle preparation and then we have measured inositol-1,4,5-trisphosphate induced calcium release from tobacco microsomal fraction. These findings suggest that phosphoinositide signaling system is present and operates in the tobacco suspension culture.e.

• The Korean Journal of Physiology and Pharmacology
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• 제21권5호
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• pp.495-507
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• 2017

The effect of clonidine administered intrathecally (i.t.) on the mortality and the blood glucose level induced by sepsis was examined in mice. To produce sepsis, the mixture of D-galactosamine (GaLN; 0.6 g/10 ml)/lipopolysaccharide (LPS; $27{\mu}g/27{\mu}l$) was treated intraperitoneally (i.p.). The i.t. pretreatment with clonidine ($5{\mu}g/5{\mu}l$) increased the blood glucose level and attenuated mortality induced by sepsis in a dose-dependent manner. The i.t. post-treatment with clonidine up to 3 h caused an elevation of the blood glucose level and protected sepsis-induced mortality, whereas clonidine post-treated at 6, 9, or 12 h did not affect. The pre-treatment with oral D-glucose for 30 min prior to i.t. post-treatment (6 h) with clonidine did not rescue sepsis-induced mortality. In addition, i.t. pretreatment with pertussis toxin (PTX) reduced clonidine-induced protection against mortality and clonidine-induced hyperglycemia, suggesting that protective effect against sepsis-induced mortality seems to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Moreover, pretreatment with clonidine attenuated the plasma tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$) induced by sepsis. Clonidine administered i.t. or i.p. increased $p-AMPK{\alpha}1$ and $p-AMPK{\alpha}2$, but decreased p-Tyk2 and p-mTOR levels in both control and sepsis groups, suggesting that the up-regulations of $p-AMPK{\alpha}1$ and $p-AMPK{\alpha}2$, or down-regulations of p-mTOR and p-Tyk2 may play critical roles for the protective effect of clonidine against sepsis-induced mortality.

• The Korean Journal of Physiology and Pharmacology
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• 제12권6호
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• pp.315-321
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• 2008

Eugenol is widely used in dentistry to relieve pain. We have recently demonstrated voltage-gated $Na^+$ and $Ca^{2+}$ channels as molecular targets for its analgesic effects, and hypothesized that eugenol acts on $P2X_3$, another pain receptor expressed in trigeminal ganglion (TG), and tested the effects of eugenol by whole-cell patch clamp and $Ca^{2+}$ imaging techniques. In the present study, we investigated whether eugenol would modulate 5'-triphosphate (ATP)-induced currents in rat TG neurons and $P2X_3$-expressing human embryonic kidney (HEK) 293 cells. ATP-induced currents in TG neurons exhibited electrophysiological properties similar to those in HEK293 cells, and both ATP- and $\alpha$, $\beta$-meATP-induced currents in TG neurons were effectively blocked by TNP-ATP, suggesting that $P2X_3$ mediates the majority of ATP-induced currents in TG neurons. Eugenol inhibited ATP-induced currents in both capsaicin-sensitive and capsaicin-insensitive TG neurons with similar extent, and most ATP-responsive neurons were IB4-positive. Eugenol inhibited not only $Ca^{2+}$ transients evoked by $\alpha$, $\beta$-meATP, the selective $P2X_3$ agonist, in capsaicin-insensitive TG neurons, but also ATP-induced currents in $P2X_3$-expressing HEK293 cells without co-expression of transient receptor potential vanilloid 1 (TRPV1). We suggest, therefore, that eugenol inhibits $P2X_3$ currents in a TRPV1-independent manner, which contributes to its analgesic effect.

• 약학회지
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• 제34권4호
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• pp.224-237
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• 1990

A single uniform population of specific, saturable, high affinity binding site of $[^3H]QNB$ guinuclidinyl benzilate(QNB) was identified in the rat cerebral microsomes. The Kd value(37.2 pM) for $[^3H]QNB$ calculated from the kinetically derived rate constants was in agreement with the Kd value(48.9 pM) determined by analysis of saturation isotherms at various receptor concentrations. Dimenhydrinate(DMH), histamine $H_1-blocker$, increased Kd value for $[^3H]QNB$ QNB without affecting the binding site concentrations and this effect resulted from the ability of DMH to slow $[^3H]QNB-receptor$ association. Pirenzepine inhibition curve of $[^3H]QNB$ binding was shallow(nH = 0.52) indicating the presence of two receptor subtypes with high ($M_1-site$) and low($M_2-site$) affinity for pirenzepine. Analysis of these inhibition curves yielded that 68% of the total receptor populations were of the $M_1-subtype$ and the remaining 32% of the $M_2-subtype$. Ki values for the $M_1-$ and $M_2-subtypes$ were 2.42 nM and 629.3 nM, respectively. Ki values for $H_1-blockers$ that inhibited $[^3H]QNB$ binding varied with a wide range ($0.02-2.5\;{\mu}M$). The Pseudo-Hill coefficients for inhibition of $[^3H]QNB$ binding by most of $H_1-blockers$ examined except for oxomemazine inhibition of $[^3H]QNB$ binding were close to one. The inhibition curve for oxomemazine in competition with $[^3H]QNB$ was shallow(nH = 0.74) indicating the presence of two receptor populations with different affinities for this drug. The proportion of high and low affinity was 33:67. The Ki values for oxomemazine were $0.045{\pm}0.016\;{\mu}M$ for high affinity and $1.145{\pm}0.232\;{\mu}M$ for low affinity sites. These data indicate that muscarinic receptor blocking potency of $H_1-blockers$ varies widely between different drugs and that most of $H_1-blockers$ examined are nonselective antagonist for the muscarinic receptor subtypes, whereas oxomemazine might be capable of distinguishing between subclasses of muscarinic receptor.

• 한국자원식물학회지
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• 제23권6호
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• pp.513-518
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• 2010

In the present study, the antinociceptive profiles of Dianthus chinensis L extract were examined in ICR mice. Dianthus chinensis L extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Dianthus chinensis L extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P ($0.7\;{\mu}g$) was diminished by Dianthus chinensis L extract. Intraperitoneal (i.p.) pretreatment with yohimbine ($\alpha_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Dianthus chinensis L extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Dianthus chinensis L extract in the writhing test. Our results suggest that Dianthus chinensis L extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Dianthus chinensis L extract may be mediated by $\alpha_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• 한국가축번식학회지
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• 제18권2호
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• pp.95-99
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• 1994

우수성이 이미 입증된 oxytocin antagonist-I(AI)이 발정된 쥐의 자궁내 옥시토신 수용체 수와 결합친화력이 어떤 영향을 미치는 지를 알아보는 것이 본 연구의 목적이었다. 마취된 흰쥐들에게 5$\mu\textrm{g}$의 AI를 투여하였으며, 30분과 4시간후에 도살하였다. 자궁조직을 회수하여 잘게 잘라 냉동시킨 다음 다시 자궁조직을 분쇄한 후 단계적인 초고속 원심분리를 거쳐 옥시토신 수용체가 있는 세포막을 추출하였다. 옥시토신 수용체 분석은 높은 활동성을 보이는 옥시토신 길항제와 방사선 동위원소가 붙지 않은 옥시토신이 경쟁하는 포화상태에서 실시하였다. 옥시토신 수용체의 수와 결합친화력은 nonlinear curve fitting 방법에 의해 계산되었다. 연구 결과, AI이 투여된 흰쥐들은 수용체의 수와 결합력에 있어서 control과 유의한 차이를 보이지 않았다(p>0.05). 결론적으로 AI은 옥시토신 수용체의 수와 결합친화력을 변화시키지 않고 다만 옥시토신과 경쟁력으로 억제하는 작용을 옥시토신 수용체에서 나타낸다는 것을 이 연구에서 입증하였다.

• Clinical and Experimental Pediatrics
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• 제53권4호
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• pp.525-531
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• 2010

목 적: 융모 위축을 보이는 FPIES 환자의 소장 점막에는 TNF-${\alpha}$의 발현이 증가한다. TNF-${\alpha}$는 상피 세포의 세포 자렴사를 유발하는 것으로 알려져 있다. 저자들은 FPIES 병리생리의 특성을 알아보고자 십이지장 점막 조직에서 TNF family와 TNF-수용체 family의 세포 자멸사를 연구하였다. 방 법: 표준화된 경구 유발 시험을 통하여 FPIES로 진단된 15례의 환자와 5례의 대조군을 대상으로 연구하였다. 세포 자멸사를 확인하기 위하여 terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) 염색을 시행하였다. 세포 자멸의 기전을 알아 보기 위해 TNF family의 TNF-${\alpha}$, Fas ligand (FasL)와 TNF-수용체 family의 TNF-related apoptosis-including ligand (TRAIL) receptor 1 (DR4), TRAIL receptor 2 (DR5), Fas를 면역조직화학으로 염색하였다. 결 과: $TUNEL^+$ 세포는 대조군에 비하여 FPIES 환자군의 십이지장 점막에서 의미 있게 높게 발현하였다($P$=0.043). TNF-${\alpha}$ ($P$=0.0001)와 DR4 ($P$=0.003)도 대조군에 비하여 FPIES군에서 의미 있게 높게 발현하였다. FasL, Fas, DR5의 발현은 두 군 모두에서 낮았으며, 두 군간에 의미 있는 차이를 보이지도 않았다. 결 론: FPIES의 병리생리는 세포 자멸사에 의하여 발생하며, TNF-${\alpha}$의 발현과 DR4 경로가 세포 자멸사에서 중요한 역할을 하는 것으로 추정된다.