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

• 약학회지
• /
• 제38권3호
• /
• pp.238-249
• /
• 1994

The purpose of this research was to investigate effects of baicalin on the differentiation of preadipocytes, 3T3-L1, and to characterize the action of baicalin that affect the responses of 3T3-L1 cells during differentiation. In various culture conditions, effects of baicalin and adrenoreceptor agonists such as phenylephrine(PE) and isoproterenol(IPR) on cell differentiation were examined. Also, effects of the drugs on differentiation, triglyceride(TG) contents, expression of insulin receptor, cAMP contents, the cytosolic $Ca^{2+}$ levels, and amount of calmodulin(CaM) were examined. The results suggest that baicalin has adrenergic receptor blocking activity during the process of differentiation of 3T3-L1 cells and that in the early stage of the adipose conversion, the effect of baicalin on the adipocyte differentiation is mediated by the regulation of insulin receptor expression, but by alterations of the cAMP and the calcium metabolism in the late stage. These results also suggest that the action of baicalin may be significant in the lipid metabolism, lipogenic and lipolytic pathways, of adipose cells.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
• /
• pp.53-53
• /
• 1993

In considering the mechanism of action of the calcium antagonists, it is important to realize that there are three distinct receptor types and that the new classification divides these three drugs as members of the dihydropyridine, phenylalkylamines and benzothiazipines, respectively. The World Health Organization as well as the International Union of Pharmacology and Cardiology have adopted this classification. Unlike every other class of drugs, such as the alpha and beta adrenergic blocking agents, diuretics, etc., the calcium antagonists need to be thought of as three distinct drug classes. The reason they share some, but not all of the pharmacological profile is that they all act at specific receptor domains present in one large protein of 165 daltons present in all excitable tissue. This protein along with several other subunits make up what is known as the voltage-dependent calcium channel (the so-called "L"type, L-VDCC). The mechanism of action of the three drugs involve first a specfic binding and then an inhibition of the movement of calcium into the cell Some of these drugs, such as diltiazem, may have other interesting intracellular effects perhaps associated with protection of the mitochondria during ischemic insults. The nature of the receptor is being explored by molecular genetic techniques, and we have recently cloned two of the major subunits; some of the data will be presented.

• 대한수의학회지
• /
• 제27권1호
• /
• pp.35-40
• /
• 1987

Higenamine, a benzyltetrahydroisopuinoline analog isolated from aconite tuber, has potent isotropic action. Recent studies suggest it may have beta receptor agonistic property in that its inotropic action is blocked by propranolol in isolated rabbit heart. However, no study has been carried out on other organs than heart. Higenamine is expected to have pharmacological actions on smooth muscle on the ground that it has catecholamine moiety and tetrahydrosioquinoline nucleus in its chemical structure, both of which are well known to have smooth muscle relaxation effects. Therefore present study was aimed at determining whether higenamine has bronchodilating effect in isolated guinea pig trachea smooth muscle rich in adrenergic beta receptor and if any, it has agonistic effect on beta receptor. The results were summarized as follows : 1. Higenamine had remarkable bronchodilating effect in guinea pig tracheal smooth muscle in a dose-dependent manner. 2. Bronchodilator effect of higenamine in isolated guinea pig tracheal smooth muscle was blocked competitively by propranolol. The $pD_2$ value of higenamine in isolated guinea pig tracheal smooth muscle was 5.65 and the $pA_2$ value of propranolol against higenamine in the same preparation was 7.97.

• Clinical and Experimental Pediatrics
• /
• 제48권6호
• /
• pp.580-587
• /
• 2005

New evidence is emerging that airway smooth muscle(ASM) may act as an immunomodulatory cell by providing pro-inflammatory cytokines and chemokines, polypeptide growth factors, extracellular matrix proteins, cell adhesion receptors and co-stimulatory molecules. ASM can promote the formation of the interstitial extracellular matrix, and potentially contribute to the alterations within the extracellular matrix in asthma. In addition, extracellular matrix components can alter the proliferative, survival, and cytoskeletal synthetic function of ASM cells through integrin-directed signaling. Increased ASM mass is one of the most important features of the airway wall remodeling process in asthma. Three different mechanisms may contribute to the increased ASM mass : cell proliferation, increased migration and decreased rate of apoptosis. The major signaling pathways of cell proliferation activated by ASM mitogens are those dependent on extracellular signal-regulated kinase and phosphoinositide 3'-kinase. The key signaling mechanisms of cell migration have been identified as the p38 mitogen-activated protein kinase and the p21-activated kinase 1 pathways. ASM cells contain ${\beta}2$-adrenergic receptors and glucocorticoid receptors. They may represent a key target for ${\beta}2$-adrenergic receptor agonist/corticosteroid interactions which have antiproliferative activity against a broad spectrum of mitogens.

• The Korean Journal of Physiology and Pharmacology
• /
• 제15권1호
• /
• pp.37-41
• /
• 2011

Interstitial cells of Cajal (ICC) evoke pacemaker activities in many tissues. The purpose of this study was to investigate the relationship between interstitial cell and pacemaker activity in the human ureter through the recording of spontaneous contractions. Spontaneous contractions of eight circular and longitudinal smooth muscle strips of the human ureter to acetylcholine (ACh) and/or norepinephrine (NE) were observed. Human ureteral strips were divided into proximal and distal groups, and each group was subdivided into circular and longitudinal groups. The proximal group showed spontaneous activities of 3~4 times within 5 minutes in the longitudinal group. ACh ($10^{-4}\;M$) augmented the frequency of the spontaneous contractions. The cumulative application of NE also augmented the frequency in a dose-dependent manner. The effects of NE application were inhibited by concomitant application of $10^{-5}\;M$ glibenclamide. Receptor tyrosine kinase (c-kit) staining revealed abundant ICCs only in proximal tissues. Therefore, spontaneous contractions of the human ureter might be modulated by ICC in the proximal region, and the actions might be related with the activation of cholinergic and/or adrenergic system mediated by a glibenclamide-sensitive pathway.

• 대한수의학회지
• /
• 제35권2호
• /
• pp.237-243
• /
• 1995

The effects of various autonomic blocking agents to perivascular nerve stimulation were investigated on isolated coronary artery of pig. 1. The magnitude of contractile response to perivascular nerve stimulation increased with increasing frequency(280Hz) of stimulation. 2. The contractions to perivascular nerve stimulation(40V, 40Hz, 0.5msec, 1min) were increased by pretreatment of the cholinestrase inhibitor, physostigmine. 3. The contraction to perivascular nerve stimulation(40V, 40Hz, 0.5msec, 1min) was antagonised by the muscarinic antagonist, atropine. 4. The contraction to perivascular nerve stimulation(40V, 40Hz, 0.5msec, 1min) was blocked by the neural blocker, tetrodotoxin. 5. The contractions to perivascular nerve stimulation(40V, 40Hz, 0.5msec, 1min) were not significantly affected by the ${\alpha}$-adrenergic antagonist, phentolamine or ${\beta}$-adrenergic antagonist, propranolol. 6. The contractile response by the acetylcholine was increased by the pretreatment of cholinestrase inhibitor, physostigmine. This findings suggest that the powerful excitatory action by the perivascular nerve stimulation may be linked to muscarinic receptor by cholinergic nerve excitation in coronary artery of pig.

• 대한약리학회지
• /
• 제5권2호
• /
• pp.115-119
• /
• 1969

The authors studied the adrenotropic receptors of isolated urinary bladder from Sebastes inermis, using adrenergic activators such as epinephrine, nor-epinephrine, isoproterenol and phenylephrine and adrenergic blocking agents such as phenoxybenzamine, pronethalol and propranolol. The studies have revealed the following results. 1) The spontaneous motility of isolated bladder from Sebastes inermis was inhibited by epinephrine nor-epinephrine, isoproterenol and phenylephrine. 2) The inhibitory effect of phenylephrine on the Sebastes inermis bladder was blocked by phenoxybensamine. 3) The inhibitory effect of isoproterenol was blocked by pronethalol and propranolol. 4) The effect of epinephrine and nor-epinephrine on the Sebastes inermis bladder was usually not blocked by either kind of blocking agent alone, but was blocked by a combination of ${\alpha}\;and\;{\beta}$ blockades. 5) It is, therefore, concluded that the Sebastes inermis bladder has alpha and that both receptors, and that both receptors subserve retaxation or inhibition.

• 대한약리학회지
• /
• 제3권1호
• /
• pp.43-49
• /
• 1967

Supplemental studies were made on the adrenotropic receptors of the rat uterus, using adrenergic activators such as phenylephrine, norepinephrine, epinephrine, and isoproterenol and adrenergic blocking agents such as phenoxybenzamine and inderal. The studies have revealed the following results : 1. Phenylephrine, norepinephrine, epinephrine, and isoproterenol inhibited the spontaneous motility of the isolated rat uterus in the following order : Isoproterenol>epinephrine>norepinephrine>phenylephrine. 2. The inhibitory responses of the isolated rat uterus to phenylephrine and epinephrine were abolished by the pretreatment with phenoxybenzamine. 3. The inhibitory responses of the isolated rat uterus to isoproterenol and epinephrine were not affected by phenoxybenzamine. 4. The motility of the isolated rat uterus pretreated with inderal was stimulated by phenylephrine, norepinephrine and epinephrine. 5. The inhibitory responses of the isolated rat uterus to isoproterenol were abolished by the pretreatment with inderal. 6. The motility of the isolated rat uterus pretreated with inderal and phenoxybenzamine was not affected by phenylephrine, norepinephrine and epinephrine. 7. It is, therefore, concluded that the rat uterus has both alpha excitatory and beta inhibitory receptors, with beta inhibitory receptors predominating.

• 대한약리학회지
• /
• 제16권2호
• /
• pp.25-29
• /
• 1980

Etomidoline ($Nonspa^{\circledR}$), which is chemically related to tertiary amine, is new synthetic antispasmodic agent with analgesic action. Antispasmodic effect of this agent is stronger than hyoscine butylbromide ($Buscopan^{\circledR}$), quaternary amine, and the absorption from intestine is also much higher. This study was undertaken to determine the effect of etomidoline on duodenal motility and other smooth muscles of rabbit. Strips of various isolated smooth muscle, 2 cm long from adult rabbits weighting about 2 kg, were suspended in a muscle chamber containing Tyrode's solution, which was bubbled with oxygen gas, and the temperature of the solution was kept constant at $38^{\circ}C$. After being washed with fresh solution several times the strips of smooth muscle attained constant motility and tonus. Etomidoline and other drugs were added in various concentrations to the chamber. Contractility of the strips was measured by using polygraph (Grass, model 7). The results are as follows: 1) In isolated rabbit atrium etomidoline produces a slight depression of contractility and the rate is also decreased. 2) On the other hand, etomidoline relaxed isolated strips of stomach, duodenal, and detrusor of rabbit. This relaxing effect of etomidoline on isolated duodenal strip of rabbit was not blocked by ${\alpha}$-adrenergic blocking agent, phenoxybenzamine, but by ${\beta}$-adrenergic blocking agent, propranolol. 3) Etomidoline did not exert any effect on isolated aorta, gall bladder, and trigone of rabbit. From the above results, it may be concluded that the relaxing effect of etomidoline on duodenal strip is related ${\beta}$-adrenergic receptor.