• Biomolecules & Therapeutics
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• 제1권1호
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• pp.1-8
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• 1993

It has been known that calcium antagonists also inhibit the radioligand binding to muscarinic and $\alpha$-adrenergic receptors and, in case of verapamil, these inhibitions may play a role in the effects of verapamil on the heart. In this study, the effects of nicardipine, nifedipine, nimodipine, diltiazem and verapamil on the binding of [$^3H$]dihydroalprenolol (DHA) to dog cardiac ${\beta}$-adrenergic receptors were examined. A single uniform [$^3H$]DHA binding site ($K_D/= 5nM\;and\;B_{max}=2600$ fmol/mg protein) was identified in dog cardiac sarcolemma. [$^3H$]DHA binding was not affected by the usual therapeutic concentrations of these calcium antagonists (nanomolar range) but in the "nonspecific"concentration ranges ($28-180{\mu}m$) these drugs inhibited [$^3H$]DHA binding to $\beta$-adrenergic receptors. Nicardipine, nifedipine, nimodipine and diltiazem competed for [$^3H$]DHA binding to ${\beta}$-adrenergic receptors with dissociation constants ($K_i$) of $28{\mu}m,\' 74{\mu}m, 39{\mu}m \;and \;35{\mu}m,$ respectively. Verapamil ($K_i=176.5 {\mu}m$) was less potent inhibitor than other drugs and this inhibition was noncompetitive; the maximal binding capacity ($B_{max}$) $300 {\mu}m$ verapamil without change in the apparent dissociation constant (4K_D$) for DHA. These results indicate that the inhibitory action of calcium antagonists at high concentrations on ${\beta}$-adrenergic receptors is not involved in the therapeutic effects of these drugs by the calcium channel blocking action.

• 대한약리학회지
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• 제13권2호
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• pp.49-59
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• 1977

Adrenergic receptors are now classified into alpha type and beta type These adrenergic receptors are distributed in various tissue in different patterns. Therefore, the adrenergic response of a certain tissue may be different from those of the other tissues, and such differences may exist among various species of animals. In this paper, the authors attempt to reevaluate the effect of epinephrine on the isolated atria, aortic strips, and vas deferenses of rabbits preincubated with alpha receptor blockades (ergotamine and dibenamine) and beta receptor blockades (propranolol and dichloroisoproterenol) in Locke-Ringer bathing medium. The results obtained were summarized as follows; 1) The dose dependent responses of isolated atria to epinephrine were significantly inhibited by propranolol and dichloroisoproterenol, and slightly inhibited by dibenamine, but not affected by ergotamine. 2) The dose dependent responses of excised aortic strips to epinephrine were significantly inhibited by ergotamine and dibenamine, but the responses were slightly potentiated by propranolol, and significantly by dichloroisoproterenol. 3) The dose dependent responses of isolated vas deferenses to epinephrine were significantly inhibited by ergotamine and dibenamine, but slightly potentiated by propranolol and dichloroisoproterenol.

• 대한약리학회지
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• 제16권1호
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• pp.9-14
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• 1980

To evaluate the adrenergic receptors for glycogenolytic responses to catecholamine, the blood glucose level, liver glycogen content and muscle glycogen level in rats were studied with treatment of epinephrine, norepinephrine and isoproterenol. In addition, to study the possibility of interconversion of adrenergic receptors, the effects of catecholamines in feeding animal were compared with those in fasting animal. The results are summarized as follow; 1) Epinephrine and norepinephine showed dose dependent increase of blood glucose level but the effect of isproterenol was not significant. 2) The prandial states of animal did not influence on effects of catecholamines on blood glucose level. 3) Liver glycogen contents were lowered by epinephrine or by norepinephrins but effect of isoproterenol was not significant. 4) Glycogen content of skeletal muscle was significantly lowered by isoproterenol and. epinephrine shifted the dose-response curve to right, but the effect of norepinephrine was not significant. 5) The effects of epinephrine and norepinephrine on blood glucose were significantly blocked by ergotamine but not by propranolol. These results indicate that the glycogenolytic response to adrenergic agents in rat is mediated by an alpha-receptor in liver and by a beta-receptor in skeletal muscle.

• 대한약리학회지
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• 제31권2호
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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.

• 대한수의학회지
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• 제39권3호
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• pp.472-477
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• 1999

To elucidate the action of the cholinergic and adrenergic nerve on isolated gastric fundus smooth muscle of rabbit, the effects of electrical transmural stimulation were investigated in the presence of atropine, cholinergic receptor blocker; phentolamine, nonselective ${\alpha}$-adrenergic receptor blocker; propranolol, nonselective ${\beta}$-adrenergic receptor blocker and L-arginine from the isometric contraction of physiological recording system. 1. The contractile response induced by electrical transmural stimulation was increased as the frequency(1~32Hz)-dependent manner on the isolated gastric fundus smooth muscle. 2. The contractile response induced by electrical transmural stimulation was markedly inhibited by the pretreatment of atropine($1{\mu}M$). 3. The contractile response induecd by electrical transmutal stimulation was inhibited by the pretreatment of phentolamine($1{\mu}M$). 4. The relaxative response induced by electrical transmural stimulation on presence of atropine ($1{\mu}M$) was inhibited by the pretreatment of propranolol($1{\mu}M$). 5. The relaxative responses on precontraction induced by histamine($10{\mu}M$) with guanethidine ($50{\mu}M$) and atropine($1{\mu}M$) by electrical transmural stimulation were increased by L-arginine (1mM). These findings suggest that it was the excitatory action of cholinergic and ${\alpha}$-adrenergic nerve, and the inhibitory action of ${\beta}$-adrenergic nerve and nonadrenergic noncholinergic nerve on the isolated gastric fundus smooth muscle of rabbit.

• 대한수의학회지
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• 제24권1호
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• pp.17-23
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• 1984

To validate the physiological properties of the histamine receptors of ileal smooth muscle in dog, the effects of adrenergic-, cholineric-, and H-receptor antagonists on the responses of ileal smooth muscle strips to histamine were investigated. The results were summarized as follows; 1. Histamine caused the contraction of ileal smooth muscle and the contractile responses were increased between the concentration of histamine $10^{-7}M$ and $10^{-5}M$ with dose-dependent manner in dog. 2. The shorter the treatment interval of histamine, the lower the contractile activity until the treatment interval extended to 40 minutes. 3. The contractile response induced by histamine was completely blocked by the pre treatment with a $H_1$-receptor blocker, chlorpheniramine and not by the pretreatment with a $H_2$-receptor blockers cimetidine. 4. The contractile response induced by histamine was not blocked by the pretreatment with a cholinergic receptor blocker, atropine. 5. The contractile response induced by histamine was not blocked by the pretreatment with an ${\alpha}$-adrenergic receptor blocker, phenoxybenzamine, or a ${\beta}$-adrenergic receptor blocker, propranolol. From these results, it was suggested that the contraction induced by histamine was elicited through $H_1$-receptor on the ileal smooth muscle in dog.

• 대한수의학회지
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• 제32권1호
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• pp.41-49
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• 1992

Higenamine is an Aconiti tuber derived compound whose chemical structure is 1-(4'-hydroxybenzyl)-6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline containing catechol ring and tetrahydroisoquinoline nucleus in its own structure, both of which are well known to have agonistic effects on adrenergic receptors. Using guinea-pig atria(rich in ${\beta}_1$-receptor) and treachea(rich in ${\beta}_2$-receptor), we studied pharmacological actions of higenamine on these organs with special interest of its relevancy of ${\beta}$-receptor selectivity. In order to further clarify its pharmacological characteristics, the influncences of pretreatment of reserpine or cocaine were also investigated. The results were summarized as follows : 1. Higenamine had remarkable chronotropic, inotropic and bronchodilator effects in guinea-pig spontaneously beating right atria, left atria and trachea, in dose-dependent manners. 2. All of above actions were blocked competitively by propranolol, which shows nonselectivity of higenamine on ${\beta}$-receptor. $pA_2$ values of propranolol against higenamine were 7.93, 7.76 and 8.46 in guinea-pig right atria, left atria and treachea, respectively. 3. Reserpine pretreatment(5mg/kg, ip, 24h) did not show my decrease in pharmacological actions of higenamine, which suggests higenamine has direct action on ${\beta}$-receptor not via catecholamine release. 4. Cocaine pretreatment$(1{\mu}M)$ had no influence on pharmacological actions of higenamine in contrast with nor epinephrine, which suggests there is no neuronal uptake mechanism of higenamine in the studied organ preparations.

• 대한약리학회지
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• 제28권1호
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• pp.75-79
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• 1992

Higenamine은 부자의 활성 성분의 하나로서 아드레나린성 beta-수용체를 통하여 강심효과를 나타내는 것으로 알려졌다. 본 연구는 norepinephrine 또는 potassium에 의한 토끼 페동맥의 수축에 미치는 Higenamine의 영향을 관찰한 것이다. 1. Norepinephrine으로 수축을 이르킨 폐동맥편은 higenamine의 전처치 또는 후처치로 용량의존적으로 이완되었다. 이같은 higenamine의 효과는 propranolol 전처치로 억제되었다. Higenamine의 propranolol에 대한 $pA_2$ 값은 8.25였다. 2. Higenamine의 페동맥편에 대한 효과는 phentolamine 전처치로 억제되지 않았다. 3. Isoproterenol도 norepinephrine에 의한 페동맥편 수축을 이완시켰으며 효력은 higenamine 보다 10배 켰다. 그러나 고농도$(3.3{\times}10^{-6})$의 isoproterenol은 내인성 활성을 보였다. 4. Higenamine과 isoproterenol은 potassium으로 유도된 페동맥편 수축에 대하여 이완효과를 나타내지 않았다. 이상의 결과로 미루어 higenamine은 혈관평활근에 대하여도 아드레나린성 beta-수용체를 통하여 이완효과를 나타낼 것으로 생각된다.

• 운동영양학회지
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• 제25권3호
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• pp.28-35
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• 2021

[Purpose] As Panax ginseng C. A. Meyer (ginseng) exhibits various physiological activities and is associated with exercise, we investigated the potential active components of ginseng and related target genes through network pharmacological analysis. Additionally, we analyzed the association between ginseng-related genes, such as the G-protein-coupled receptors (GPCRs), and improved exercise capacity. [Methods] Active compounds in ginseng and the related target genes were searched in the Traditional Chinese Medicine Database and Analysis Platform (TCMSP). Gene ontology functional analysis was performed to identify biological processes related to the collected genes, and a compound-target network was visualized using Cytoscape 3.7.2. [Results] A total of 21 ginseng active compounds were detected, and 110 targets regulated by 17 active substances were identified. We found that the active compound protein was involved in the biological process of adrenergic receptor activity in 80%, G-protein-coupled neurotransmitter in 10%, and leucocyte adhesion to arteries in 10%. Additionally, the biological response centered on adrenergic receptor activity showed a close relationship with G protein through the beta-1 adrenergic receptor gene reactivity. [Conclusion] According to bioavailability analysis, ginseng comprises 21 active compounds. Furthermore, we investigated the ginseng-stimulated gene activation using ontology analysis. GPCR, a gene upregulated by ginseng, is positively correlated to exercise. Therefore, if a study on this factor is conducted, it will provide useful basic data for improving exercise performance and health.

• 한국동물위생학회지
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• 제18권3호
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• pp.29-35
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• 1995

The effects of prostaglandin $F_2{\alpha}$ were investigated on the uterine smooth muscle motility in the pig. The results were summarized as follows : 1. Prostaglandin $F_2{\alpha}$ caused the contraction of the porcine uterine smooth muscle and the contractile responses increased between the concentration of prostaglandine $F_2{\alpha}$ $10^{-9}$ M and $5{\times}10^{-8}$ M with a dose-dependent manner. 2. The contractile response induced by prostaglandine $F_2{\alpha}$($10^{-8}$ M) was not blocked by pre-treatment with cholinergic receptor blocker, atropine ($10^{-6}$ M). 3. The contractile response induced by prostaglandine $F_2{\alpha}$(10$^{-8}$ M) was not blocked by pretreament with ${\alpha}$-adrenergic receptor blocker, phentolamine($10^{-6}$ M) and ${\beta}$-adrenergic receptor blocker, propranolol($10^{-6}$ M). From these results, it was concluded that the effects of uterine smooth muscle by prostaglandine $F_2{\alpha}$ were only the contraction mediated by prostaglandine TEX>$F_2{\alpha}$ receptor in pig, and that it may not be related to the cholinergic and adrenergic receptor.