• The Korean Journal of Physiology
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• v.20 no.2
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• pp.249-256
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• 1986

The present study was performed to investigate a possible influence of the adrenergic nervous system on pancreatic exocrine secretion stimulated by intraduodenal acid perfusion. Pancreatic secretion was collected in rats anesthetized with urethane after 24 hours fasting. The duodenal lumen was perfused (0.2 ml/min) with HCI solution in a concentration of 0.005, 0.01, 0.02, 0.05 or 0.1 N When the volume of panceratic juice secreted for IS min became constant phentolamine (1 mg/kg), $noradrenaline\;(10\;{\mu}g/kg),\;Propranolol\;(1\;mg/kg),\;and \;isoproterenol\;(1\;{\mu}g/kg)$ were administered through the jugular vein in bolus. The secretory volume and protein output were measured in the pancreatic juice collected for 15 min. 1) HCI, perfused intraduodenally in graded concentrations from 0.005 N to 0.1 N, increased the pancreatic secretory volume and protein output dose-dependently. 2) In the basal state as well as in the stimulated state by the duodenal acid perfusion, phentolamine increased the pancreatic secretory volume and protein output while propranolol inhibited the volume and protein output. 3) In the basal state, noradrenaline did not change the pancreatic secretory volume but increased the protein output while isoproterenol increased both of the secretory volume and the protein output. These results strongly suggest that ${\alpha}-adrenoceptors$ in the rat pancreas exert an inhibitory influence on the pancreatic exocrine secretion including volume and protein output in the basal state as well as in the stimulated state by the intraduodenal acid perfusion while ${\beta}-adrenoceptors$ play a stimulatory role in the pancreatic exocrine secretion. However, in the physiological situation, adrenergic excitation may stimulate the protein output through ${\beta}-adrenoceptors$ without change in the secretory volume in the rat pancreas.

• The Korean Journal of Physiology
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• v.19 no.2
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• pp.189-202
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• 1985

Enhanced activity of renin-angiotensin-aldosterone system has been suggested as a cause of the high blood pressure in certain forms of experimental hypertension. In spontaneously hypertensive rats, however, increased activity of the system has not been found, and even suppressed renin angiotensin system has been reported in the spontaneously hypertensive rat. In the present experiments it was attempted to explore the possible alteration of the short loop negative feedback control in the hypertensive rat. Experiments have been done in the anesthetized spontaneously hypertensive rats(SHR) as well as in normotensive Wistar and Sprague Dawley rats as control. Responses of the plasma renin activity to the intravenous L-isoproterenol were dose dependent, in both SHR and normotensive control rats. Hypotensive responses to smaller do sea of L-isoproterenol were more accentuated in SHR than in the normotensive control rats. Angiotensin If given intravenously suppressed plasma renin activity in a dose dependent fashion in both groups. However, these suppressive responses were significantly attenuated in SHR as compared with the normotensive control rats. Treatment with angiotensin I-converting enzyme inhibitor did not correct the attenuated responses of the plasma renin activity to angiotensin II in SHR. Intravenous infusion of arginine vasopressin also produced a dose-dependent suppression of plasma renin activity in both groups. The responses to arginine vasopressin were also significantly attenuated to the normotensive control rats. In the sodium-depleted SHR, arginine vasopressin did not suppress plasma renin activity, whereas the suppressive responses to arginine vasopressin in the normotensive control rats were not different from the untreated control rats. These data suggest that there may be a derangement in the short loop negative feedback control of the renin-angiotensin system in spontaneously hypertensive rat.

• The Korean Journal of Physiology
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• v.29 no.1
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• pp.39-50
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• 1995

This study was designed to clarify the action of cyclic nucleotides, cyclic AMP and cyclic GMP, on phorbol 12,13-dibutyrate (PDBu)-induced contraction in rings isolated from rabbit carotid artery. Arterial rings, 2 mm in width, were myographied isometrically in an isolated organ bath. PDBu produced slowly developing, sustained contraction in rabbit carotid artery, in a dose dependent manner, which was independent of extracellular $Ca^{2+}$ PDBu-induced contraction was relaxed by staurosporine, which suggests that PDBu-induced contraction is mediated by protein kinase C (PKC). $^{45}Ca^{2+}$ uptake by rabbit carotid artery was increased by PDBu during depolarization, but not in control. Isoproterenol and sodium nitroprusside (SNP) relaxed phenylephrine-induced contraction. However, SNP but not isoproterenol relaxed the contraction induced by PDBu. Acetylcholine relaxed PDBu-induced contraction in the presence of the endothelium. 8-bromo-cyclic AMP, a permeable analogue of cyclic AMP, suppressed phenylephrine-induced contraction but not PDBu-induced contraction. 8-bromo cyclic GMP relaxed both of them with dose dependency. A large dose of forskolin relaxed PDBu-induced contraction. PDBu increased cyclic AMP without considerable change in the level of cyclic GMP. Based on these findings, PDBu-induced contraction of rabbit carotid artery was relaxed by cyclic GMP more effectively than cyclic AMP, and the action of cyclic AMP could be mediated by cyclic GMP dependent protein kinase. Therefore it is suggested that the antagonistic action between protein kinase C and cyclic GMP-dependent protein kinase plays a major role in the regulation of vascular tone.

• The Korean Journal of Physiology
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• v.20 no.1
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• pp.89-102
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• 1986

It has long been suggested that the change of renin-angiotensin system is responsible for the increased arterial blood pressure in the experimental hypertension. But the exact nature of the cause and maintenance of early and late Phase of renal hypertension is still controversial. Increased renin-angiotensin system has been suggested. To clarify the altered renin-angiotensin system in the early phase of two kidney one clip Goldblatt hypertension(2K1C GH), experiments were carried out in the rats of 3,7, and 14 days of 2K1C GH rats, sham-operated, and control rats. Responses of the plasma renin activity to the intravenous infusion of L-isoproterenol were dose-dependent. Responses of the plasma renin activity to the intravenous L-isoproterenol in 2K1C GH rats were not different from sham-operated control rats. Hypotensive responses of the 2K1C GH rats were not different from sham-operated rats. Suppression by intravenous infusion of angiotensin II of plasma renin activity showed a dose-dependent manner. Suppression by angiotensin ll of plasma renin activity was attenuated or abolished in the early phase of 2K1C GH rats. Intravenous infusion of arginine vasopressin(AVP) showed a dose-dependent suppression of plasma renin activity, Attenuated responses by AVP of plasma renin activity were noticed in the early phase of 2K1C GH rats. These results suggest that the altered renin-angiotensin system in the early phase of the two kidney one clip Goldblatt hypertension may be caused by failure of the short loop negative feedback control mechanism.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.219-231
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• 1995

Vasoactive intestinal polypeptide(VIP) and ${\beta}-adrenergic$ agonists have immunomodultory effects on the peripheral blood T-lymphocytes of rat through their own receptors. Both of them utilize the same signal transduction pathway. That is, the stimulatory guanine nucleotide binding protein(G protein) mediates the receptor-adenylyl cyclase coupling, producing intracellular increase of cyclic adenosine monophosphate(cAMP). In the previous experiment, propranolol, a ${\beta}-adrenergic$ receptor blocker, inhibited the VIP-induced protein phosphorylation in lymphocytes. However, propranolol could not block the effect induced by forskolin. Therefore, this study was designed to elucidate the mechanism of the inhibitory action of propranolol on the effects of VIP. Using peripheral blood lymphocytes of rats, the effect of propranolol on the receptor binding characteristics of VIP was observed. And the effects of propranolol were compared to the effects of timolol on the cAMP increase induced by isoproterenol, VIP or forskolin. The results obtained are as follows. 1) Receptor binding study showed no significant differences in the affinity or density of VIP receptor between the control and propranolol-pretreated groups. 2) VIP-induced increase of cAMP was inhibited by propranolol, but not by timolol. 3) Both propranolol and timolol suppressed the isoproterenol-induced cAMP increase. 4) Propranolol also inhibited the histamine-induced cAMP increase. 5) Propranolol did not inhibit the increase of cAMP stimulated by forskolin. 6) Lidocaine did not block the VIP-induced cAMP increase. These results show that the inhibitory mechanism of propranolol is not related to ${\beta}-adrenergic$ receptor or its membrane stabilizing effect, and it is suggested that propranolol can block the effects of VIP by inhibiting the intermediate step between the VIP receptor and adenylyl cyclase.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.75-84
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• 2023

This study aimed to observe the protective effect of momordicine I, a triterpenoid compound extracted from momordica charantia L., on isoproterenol (ISO)-induced hypertrophy in rat H9c2 cardiomyocytes and investigate its potential mechanism. Treatment with 10 μM ISO induced cardiomyocyte hypertrophy as evidenced by increased cell surface area and protein content as well as pronounced upregulation of fetal genes including atrial natriuretic peptide, βmyosin heavy chain, and α-skeletal actin; however, those responses were markedly attenuated by treatment with 12.5 ㎍/ml momordicine I. Transcriptome experiment results showed that there were 381 and 447 differentially expressed genes expressed in comparisons of model/control and momordicine I intervention/model, respectively. GO enrichment analysis suggested that the anti-cardiomyocyte hypertrophic effect of momordicine I may be mainly associated with the regulation of metabolic processes. Based on our transcriptome experiment results as well as literature reports, we selected glycerophospholipid metabolizing enzymes group VI phospholipase A₂ (PLA2G6) and diacylglycerol kinase ζ (DGK-ζ) as targets to further explore the potential mechanism through which momordicine I inhibited ISO-induced cardiomyocyte hypertrophy. Our results demonstrated that momordicine I inhibited ISO-induced upregulations of mRNA levels and protein expressions of PLA2G6 and DGK-ζ. Collectively, momordicine I alleviated ISO-induced cardiomyocyte hypertrophy, which may be related to its inhibition of the expression of glycerophospholipid metabolizing enzymes PLA2G6 and DGK-ζ

• The Korean Journal of Pharmacology
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• v.22 no.1 s.38
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• pp.34-44
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• 1986

In our previous studies, we had clarified many pharmacological effects of majarine: the bacteriostatic effect in vitro; the potentiation of hypnotic action of alcohol; hypotensive effect in rats and hypothermic effect in mice. This study was undertaken to search for a new antihypertensive drug. Red crystalline was obtained from majarine (which was extracted from Berberis koreana Palibin) by chemical methods. And this crystalline was identified as $C_{19}H＿{16}NO＿4$ contained one hydroxy group instead of methoxy group of majarine in isoquinoline ring and named 'Majarol' (5,6-Dihydro-9-hydroxy, 10-methoxybenzo-[g]-1,3-benzodioxolo [5,6-a] quinolizinium). We examined the effects of majarol on blood pressure and heart rate in urethane ancsthetized rats and the rate and amplitude of contraction of isolated frog heart. Several drugs: atropine sulfate, diphenhydramine chloride, hexamethonium bromide, phentolamine, epinephrine, propranolol and isoproterenol were used to clarify the mechanism of the hypotensive action of majarol. The results of experimints were as follows; 1. In low dose (0.5-2mg/kg, i.v.), majarol showed a typical transient hypotensive effect and slight decrease in heart rate. In high dose (5-10 mg/kg, i.v.), majarol showed a typical transient and a subsequent prolonged hypotensive effect and a significant prolonged decrease in heart rate was followed. 2. The hypotensive effects of majarol was not abolished by the pretreatments with atropine sulfate, hexamethonium bromide and diphenhydramine. The pretreatment with phentolamine inhibited significantly the hypotensive effects of majarol and the pretreatment wtih majarol blocked markedly the hypertensive effect of epinephrine. The positive chronotropic effect of isoproterenol was not blocked by the pretreatment with majarol. 3. In low dose, majarol increased the amplitude and decreased rate of contraction, but in high dose, majarol inhibited the amplitude and rate of contraction of isolated frog heart.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.97-105
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• 1993

Adenosine receptors in rat adipose tissues have been reported to be of $A_{1}$ subclass, and their stimulation leads to inhibition of adenylyl cyclase, resulting in inhibition of lipolysis. In the present study we investigated changes in $A_{1}$ adenosine receptor-adenylyl cyclase system of adipocytes following induction of experimental diabetes in rats. One week following experimental diabetes were induced by intravenous injection of streptozotocin (50 mg/kg body wt.), adipocytes from rats $(170{\sim}230g)$ fed ad libitum were isolated using collagenase. When adipocytes were incubated for 1 h with 1 unit/ml adenosine deaminase and $1\;{\mu}M$ isoproterenol, and assayed for glycerol formation, it was found that the inhibition of lipolysis in diabetic adipocytes by $(-)-N^{6}-(R-phenylisopropyl)adenosine$ (PIA), an $A_{1}$, adenosine receptor agonist, was twice that of control adipocytes. In an effort to delineate the mechanism(s), $[^{3}H]PIA$ binding to adipocytic membranes from diabetic and control rats were determined. Neither the affinities nor numbers of $A_{1}$ adenosine receptor were significantly different from each other (Best fit parameters for the one-site model are: $K_{d}=0.51{\pm}0.09nM$ and $B_{max}=1.60{\pm}0.12\;pmoles/mg$ protein for control membranes; $K_{d}=0.54{\pm}0.21\;nM$ and $B_{max}=1.72{\pm}0.31\;pmoles/mg$ protein for diabetic membranes). However, the inhibiton by PIA of the isoproterenol-stimulated adenylyl cyclase activities was found to be 1.9 times higher in adipocytic membranes from diabetic rats than those from controls. These results suggest that the increased sensitivity of inhibition of lipolysis to PIA in adipocytic membranes from diabetic rats is due to changes in signal transduction pathways, rather than alterations of $A_{1}4 adenosine receptor molecules themselves.

• YAKHAK HOEJI
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• v.17 no.2
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• pp.103-110
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• 1973

In this study the effect of alcohol extract of atractlis (AAE) on the blood pressure of the rabbit was investigated. The results of the experiment are as follows. AAE elicited hypotension with doses ranging from 3 to 30 mg/kg, i.v., exhibiting a linear dose-relationship. This effect of AAE was abolished by atropine and potentiated by physostigmine, while not affected by diphenhydramine, hexamethonium, propranolol and cyproheptadine. AAE did not influence the pressor responses to norepinephrine and the depressor to isoproterenol. The above results indicate that AAE produced the hypotension by stimulating the parasympathetic nervous system related to acetylcholine.

• Journal of Nutrition and Health
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• v.30 no.3
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• pp.244-251
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• 1997

The effects of Artemisia princeps var orientalis(mugwort), Circium japonicum var ussuriense (Unggungqui) on cadiovascular system in hyperlipidemic rats were investgated. Thirty rats devided into 5 experimental groups, were fed with the diet contained 1% chlesterol, 0.25% sodium cholate, 10% coconut oil and 5% lard by the same method of previous paper1). Contractile and relaxation responses in the isolated artria and thoracic aortae were measured and the morphological changes of the aortic endotherium from the rats were inspected. The responses of the right atrial to isoproterenol were significantly lower value in Ungungqui powder diet group(UP) and mugwort powder diet group(MP) than the control. The contraction force by injectin of phenylephrine and calcium in isolated thoracic aortae was significantly low value in the UP and the MP groups compaired to the control. The relaxation rate by acetylcholine in isolated thoracic aortae represented significantly higher value in UP than control. The morphological changes of endothelial cell suface was smallest in UP and the damage of endothelium by retarded in MP. Although Ungungqui and mugwort extract diet groups(UE, ME) were advanced, those were less than control.