• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.351-356
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• 1997

This study was performed in order to investigate the effect of renal denervation on diuretic action of UK 14, 304, $\alpha$$_2$-Adrenergic Agonist, administered into the vein and the carotid artery in dog. The diuretic action of UK 14, 304 administered into the vein or the carotid artery was reversed to the antidiuretic action by renal denervation, this time, the decrease of N $a^{+}$excretion amounts in urine ( $E_{Na}$ ) and the increase of N $a^{+}$ reabsorption rates in renal tubule ( $R_{Na}$ ) were exhibited. This results suggest that central diuretic action of UK 14, 304 is mediated by renal nerves and the antidiuretic action of UK 14, 304 in denervation kidney is caused by the increase of N $a^{+}$reabsorption rates ( $R_{Na}$ ) in renal tubules in dog.n dog.

• The Korean Journal of Pharmacology
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• v.22 no.1 s.38
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• pp.24-33
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• 1986

To ascertain the existence of various adrenoceptors involved in active transport of sodium in the frog skin and to delineate their physiological roles, the influence of various adrenergic agonists and antagonists on the potential difference (PD), short-circuit current (SCC) and total skin conductance (TSC) of the isolated frog skin of Rana nigromaculata were investigated. PD and SCC were determined with Ussing's technique. Drugs were administered to the serosal side of the skin. Experimental results were summarized as follows: 1. The responses to norepinephrine (NE, $6{\times}10^{-8}-6{\times}10^{-5})M$), phenylephrine (PE, $5{\times}10^{-6}-5{\times}10^{-4}M$) and epinephrine (Epi, $5.5{\times}10^{-7}-5.5{\times}10^{-5}M$) were characterized by marked elevation of PD & SCC in dose-related fashion, but the maximal effect attained by Epi was less than those of NE and PE. 2. These increments of PD & SCC were significantly inhibited by prazosin $(2{\times}10^{-6}M)$, a speciflc ${\alpha}_1$-adrenoceptor blocker. The stimulatory effect on PD & SCC were completely abolished by phenoxybenzamine (PBZ, $3.3{\times}10^{-5}M$), an irreversible ${\alpha}$-adrenoceptor blocking agent. Furthermore, with a larger doses of Epi produced marked decline of PD & SCC after the PBZ pretreatment. 3. Isoproterenol (ISP), a ${\beta}$-adrenoceptor agonist, in concentrations ranging from $5{\times}10^{-7}$ to $5{\times}10^{-6}M$ produced dose-related decrease in PD & SCC, which could be abolished by pretreatment with propranolol $(4{\times}10^{-6}M)$, a specific ${\beta}$-adrenoceptor blocker. It was further noted that the effects of Epi on PD & SCC were markedly potentiated by Propranolol pretreatment. 4. Clonidine as well as guanabenz produced increases in PD & SCC and these effects were inhibited more specifically by prazosin pretreatment than by yohimbine. These results indicated that there exist in the frog skin two distinctive types of adrenoceptors, ${\alpha}$ and ${\beta}$, which roughly corresponds to those in mammals, and that the ${\alpha}$ type of adrenoceptors mediate the stimulation of PD & SCC, whereas ${\beta}$-adrenoceptors mediate the inhibition. However, based on evidence at hand, no conclusion could be drawn on the subtype of ${\alpha}$-adrenoceptors which is involved in the stimulation of sodium transport in the frog skin.

• Archives of Pharmacal Research
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• v.9 no.4
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• pp.219-222
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• 1986

Dose-dependent increasesin blood glucose were produced by epinephrine and clonidine in fasted male mice. Isoproterenol was ineffective in increasing blood glucose at lower doses ($10^{-8}M$/kg-$10^{-7}M$/kg); with higher dose ($10^{-6}M$/kg) the glucose level was increased. The hyperglycemia induced by epinephrine was inhibited by yobimbine, prazosin and propranolol, indicating that the hyperglycemic effect of epinephrine is mediated by alpha-1, alpha-2 and beta adrenoceptor. When clonidine (10$^{-6}$ M/kg) was administered simultaneously with sioproterenol ($10^{-6}M$/kg), an enhenced hyperglycemic effect was observed. The increment produced by clonidine plus isoproterenol was higher than that by clonidine alone. These increment produced by clonidine plus isoproterenol was higher than that by clonidine alone. These results suggest that stimulation of alpha-2 adrenoceptor may be reponsible for the exertion of the hyperglycemic effect by beta agonists in fasted mice.

• Journal of Veterinary Clinics
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• v.23 no.4
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• pp.421-426
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• 2006

The effects of transmural nerve stimulation induced releasing neurotransmitters on the changes of swine uterine smooth muscle motility were examined by polygraph through isometric force transducer. The frequency dependent relaxation and rebound contraction were revealed on precontraction with histamine by transmural nerve stimulation. The rebound contraction by transmural nerve stimulation was inhibited by nonselective ${\alpha}$-adrenergic receptor antagonist, phentolamine, and the relaxation by transmural nerve stimulation was blocked by nonselective ${\beta}$-adrenergic receptor antagonist, propranolol. The relaxation induced by nonselective ${\beta}$-adrenergic receptor agonist, isoproterenol on precontraction with histamine were the dose dependent manner and this relaxation was blocked by nonselective ${\beta}$-adrenergic receptor antagonist, propranolol in isolated uterine smooth muscle of pig. These results suggest that endogenous neurotransmitters on smooth muscle relaxation was influenced by ${\beta}$-adrenergic receptor in swine.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.6
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• pp.753-761
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• 1998

Preconditioning of a heart with small doses of catecholamines induces a tolerance against the subsequent lethal ischemia. The present study was performed to find a specific receptor pathway involved with the catecholamine preconditioning and to test if adenosine plays a role in this cardioprotective effect. Isolated rat hearts, pretreated with small doses of ${\alpha}-\;or\;{\beta}-adrenergic$ agonists/antagonists, were subjected to 20 minutes ischemia and 20 minutes reperfusion by Langendorff perfusion method. Cardiac mechanical functions, lactate dehydrogenase and adenosine release from the hearts were measured before and after the drug treatments and ischemia. In another series of experiments, adenosine $A_1\;or\;A_2$ receptor blockers were treated prior to administration of adrenergic agonists. Pretreatments of a ${\beta}-agonist,\;isoproterenol(10^{-9}{\sim}10^{-7}\;M)$ markedly improved the post-ischemic mechanical function and reduced the lactate dehydrogenase release. Similar cardioprotective effect was observed with an ?-agonist, phenylephrine pretreatment, but much higher $concentration(10^{-4}\;M)$ was needed to achieve the same degree of cardioprotection. The cardioprotective effects of isoproterenol and phenylephrine pretreatments were blocked by a ${\beta}_1-adrenergic$ receptor antagonist, atenolol, but not by an ${\alpha}_1-antagonist,$ prazosin. Adenosine release from the heart was increased by isoproterenol, and the increase was also blocked by atenolol, but not by prazosin. A selective $A_1-adenosine$ receptor antagonist, 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) blocked the cardioprotection by isoproterenol pretreatment. These results suggest that catecholamine pretreatment protects rat myocardium against ischemia and reperfusion injury by mediation of ${\beta}_1-adrenergic$ receptor pathway, and that adenosine is involved in this cardioprotective effect.

• Korean Journal of Biological Psychiatry
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• v.7 no.1
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• pp.80-84
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• 2000

Background : Hypersalivation can be a troublesome side effect of clozapine, limiting its usefulness in the management of some cases of schizophrenia. But the pharmacodynamic basis of clozapine-induced hypersalivation remains obscure. Object : The aim of this study was to evaluate the effect of the ${\alpha}_2$-adrenergic agonist clonidine on clozapine-induced hypersalivation in the patients who were receiving clozapine. Method : Twenty one schizophrenic inpatients on clozapine participated in the study. The amount of saliva was measured on the 7th day at 8pm after starting clozapine treatment. Of them, 15 patients who had experienced hypersalivation was treated with 0.1mg/day of clonidine. Result : Of 21 schizophrenic patients treated with clozapine in the psychiatric inpatient clinic, 15(71.4%) complained hypervalivation. After clonidine treatment, mean salivary flow-rate was decreased significantly in these patients. Conclusion : Clozapine-induced hypersalivation could be decreased by administration of ${\alpha}_2$-adrenergic agonist clonidine and compliance could be improved. Also our study supports the notion that increased adrenergic tone contributes to clozapine-induced hypersalivation.

• The Korean Journal of Pain
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• v.9 no.2
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• pp.318-325
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• 1996

Background: Sympathectomy relieves pain in sympathectically maintained pain, and subcutaneous injection of norepinephrine(NE) can rekindle mechanical allodynia. However, the mechanism of rekindling is not clear. The purpose of this study is to investigate which subtype of $\alpha$-adrenoceptor is involved in NE-induced rekindling of mechanical allodynia in sympathectomized neuropathic rats. Methods: Neuropathic injury was produced by tightly ligating the left L5 and L6 spinal nerves of 36 male Sprague-Dawley rats and bilateral lumbar sympathectomy was done at two weeks postoperatively. Starting at 7 days after sympathectomy, rekindling of mechanical allodynia was induced by NE and clonidine injected into the left paw, which was reversed by pretreatment of phentolamine and idazoxan. Mechanical allocynia was quantified by measuring the frequency of foot lifts to two von Frey filaments applied to the paw. Results: All tested rats displayed well-developed signs of mechanical allodynia at the left paw that were abolished by a bilateral lumbar sympathectomy. Subcutaneous (s.c.) injection of NE (0.05 ${\mu}g$) into the affected paw of sympathectomized neuropathic rats rekindled previous mechanical allodynia. These effects could be mimicked by an ${\alpha}_2$-receptor agonist clonidine, but not by an ${\alpha}_1$-receptor agonist phenylephrine. The NE-induced rekindling of mechanical allodynia was significantly reduced by prior s.c. injection of a mixed $\alpha$-receptor antagonist phentolamine (20${\mu}g$) and ${\alpha}_2$-receptor antagonist idazoxan(20${\mu}g$), but not by a ${\alpha}_1$-receptor antagonist terazosin (20${\mu}g$). The pretreatment of idazoxan produced dose-related inhibition of NE-induced rekindling of mechanical allodynia. The rekindling induced by ${\alpha}_2$-receptor agonist clonidine (5${\mu}g$) was also reversed by prior s.c. injection of ${\alpha}_2$-receptor antagonist idazoxan (20${\mu}g$). Conclusion: Subcutaneous injection of NE into the paw of sympathectomized neuropathic rats rekindles mechanical allodynia, which is reversed by an ${\alpha}_2$-, but not by an ${\alpha}_1$-receptor antagonist. Therefore, rekindling of mechanical allodynia in sympathectomized neuropathic rats is mediated by ${\alpha}_2$-adrenoceptor.

• Asian-Australasian Journal of Animal Sciences
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• v.7 no.3
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• pp.397-400
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• 1994

The effect of xylazine administration on plasma cortisol, prolactin, glucose and packed cell volume (PCV) responses to immobilization and heat stress was investigated. Immobilization of rats for 2 hours by ligation of the fore and hind legs strongly caused approximately two-fold increase in plasma cortisol and prolactin levels. Plasma glucose and PCV were not significantly changed. Pretreatment of immobilized rats with xylazine (20 mg/kg body weight i.m.) resulted in approximately 20% reduction in both plasma cortisol and prolactin concentrations. A marked hyperglycemia and increase in the PCV value was observed. On the other hand, rats exposed to acute heat stress ($40^{\circ}C$, and 60% relative humidity) for 2 hours, also developed two fold increase in both plasma cortisol and prolactin concentrations and the pretreatment with xylazine caused a 20% reduction in the levels of both hormones. Plasma glucose level was not significantly changed in heat stressed rats but it was markedly increased after pretreatment with xylazine. PCV was significantly incrcased under heat stress and pretreatment with xylazine induced a pronounced elevation in this value. It was suggested that stimulation of cortisol and prolactin secretion in response to immobilization or heat stress can be partially reduced by an alpha 2-adrenergic agonist.

• Proceedings of the Korean Biophysical Society Conference
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• 1997.07a
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• pp.27-27
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• 1997

The effects of $a_1$-adrenoceptor stimulation on intracellular $Ca^{2+}$ ([C $a^{2+}$]$_{i}$ ) transient, contraction, and L-type $Ca^{2＋}$ current ( $I_{Ca,L}$) were studied in single cells isolated from ventricles of guinea pig hearts. Phenylephrine, $\alpha$$_1$-adrenergic agonist, (5$\times$10$^{-5}$ ~10$^{-4}$ M) produced a biphasic pattern of inotropism： transient negative response (decrease in contraction by 23.9$\pm$2.5% of control) followed by a sustained positive response (increase in contraction by 60.0$\pm$3.4%, mean $\pm$ SD, n=12).(omitted)ted)

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.3
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• pp.149-155
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• 2003

The aim of the present study was to examine the effects of platycodin D and $D_3$, which are active components derived from the roots of Platycodon grandiflorum A. DC., on the contractile force of the i3olated rat aorta and blood pressure of the anesthetized rat, and also to elucidate its mechanism of action. Both phenylephrine (an adrenergic ${\alpha}1$-receptor agonist) and high potassium (a membranedepolarizing agent) caused great contractile responses in the isolated aortic strips. Platycodin D at high concentration $(24{\mu}g/ml)$ inhibited contractile responses induced by phenylephrine $(10^{-5}\;M)$ and high potassium $(5.6{\times}10^{-2}\;M)$, while low concentrations of platycodin D $(4{\sim}8{\mu}g/ml$) did not affect those responses. However, platycodin $D_3\;(8{\sim}32{\mu}g/ml)$ did not alter the contractile responses evoked by phenylephrine and high $K^+$. Interestingly, the infusion of platycodin $D_3$ (1.0 mg/kg/30 min) significantly reduced the pressor responses induced by intravenous norepinephrine. However, platycodin $D_3$ (1.0 mg/kg/30 min) did not affect them. Taken together, these results show that intravenously administered platycodin D depresses norepinephrine-induced pressor responses in the anesthetized rat, at least partly through the blockade of adrenergic ${\alpha}1$-receptors. Platycodin D also caused vascular relaxation in the isolated aortic strips of the rat via the blockade of adrenergic ${\alpha}1$-receptors, in addition to an unknown direct mechanism. However, platycodin $D_3$ did not affect both norepinephrine-induced pressor responses and the isolated rat aortic contractile responses evoked by phenylephrine and high potassium. Based on these results, there seems to be much difference in the mode of action between platycodin D and platycodin $D_3$.