• YAKHAK HOEJI
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• v.35 no.4
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• pp.295-300
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• 1991

Ralationship between noradrenergic nervous system activity and luteinizing hormone releasing hormone(LHRH) content mediated by testosterone in hypothalamus was tested. Three groups of adult male animals were prepared; (1) Intact; (2) Castration+Vehicle (Cast+V); (3) Castration+Testosterone (Cast+T). Silastic capsule containing vehicle or testosterone was implanted into neck region of animals two weeks following castration. Norepinephrine content, alpha-adrenergic receptor binding characteristics using H$^{3}$-WB4101, and content of LHRH by LHRH RIA procedure were determined. Testosterone replacement to castrated male rats augmented the content of norepinephrine and LHRH. Testosterone replacement increased the alpha-adrenergic receptor density but did not change alpha-receptor affinity. The data from the present study suggest that increase in LHRH content by testosterone may be positively coupled to the activity of central noradrenergic nervous system.

• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.189-199
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• 1996

Myocardial ${\alpha}_1-adrenoceptors$ have been shown to mediate a biphaslc inotropic response that was characterized by a transient decline followed by a sustained increasing phase in guinea pig ventricular muscle. Recently one group reported that an ${\alpha}_1-adrenoceptors-induced$ intracellular $Na^+$ decrease is linked to fast $Na^+$ channel inhibition and another group reported that it is linked to $Na^+$-$K^+$ pump activation by ${\alpha}_{1b}-adrenoceptors$. But until now, its mechanism is not clear. Therefore, to see whether the $Na^+$channel or $Na^+-K^+$ pump is related to a decrease in intracellular $Na^+$ activity and/or the negative inotropic response, and which ${\alpha}_1-adrenoceptor$ subtype was involved in the decrease in intracellular $Na^+$activity by phenylephrine, we used conventional and sodium selective microelectrodes, and tension transducer to determine the effects of ${\alpha}_1-adrenergic$ stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force in guinea pig ventricular muscles. $10^{-5}$ M Phenylephrine produced a slight hyperpolarization of the diastolic membrane potential, a decrease or increase in $a_N^i_a$, and a biphasic inotropic response. The negative inotropic response accompanied by a decrease in intracellular $Na^+$activity, whereas in muscles showing a remarkable positive inotropic response without initial negative inotropic effect was accompanied by an increase in intracellular $Na^+$ activity. The decrease in intracellular $Na^+$ activity was apparently inhibited by WB4101, an antagonist of the ${\alpha}_{1a}-adrenoceptors$. The decrease in intracellular $Na^+$ activity caused by phenylephrine was not abolished or reduced by a block of the fast $Na^+$ channels. $V_{max}$ also was not affected by phenylephrine. Phenylephrine produced an increase in intracellular $Na^+$ activity in the presence of a high concentration of extracellular $Ca^{2+}$ (in quiescent muscle) or phorbol dibutyrate, a protein kinase C activator(in beating muscle). These suggest that the ${\alpha}_{1a}-adrenoceptors-mediated$ decrease in intracellular $Na^+$ activity may be related to the protein kinase C.

• Korean Journal of Veterinary Research
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• v.38 no.3
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• pp.508-517
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• 1998

There is evidence that the sympathetic nervous system exerts a control on thyroid function via an adrenergic innervation of thyroid cells. Although it is clear that the inhibitory effects of catecholamines result from an activation of ${\alpha}_1$-adrenoceptors, the mechanisms involved in ${\alpha}_1$-stimulation are not fully understood. The effects of methoxamine and protein kinase C (PKC) activator on the release of thyroxine ($T_4$) from mouse thyroid were studied to clarify the role of PKC in the regulation of $T_4$ release in vitro. The glands were incubated in the medium, samples of the medium were assayed for $T_4$ by EIA kits. Methoxamine inhibited the TSH-stimulated $T_4$ release. This inhibition was reversed by prazosin, an ${\alpha}_1$-adrenergic antagonist. Futhermore, the inhibitory effect of methoxamine on the $T_4$ release stimulated by TSH was prevented by chloroethylclonidine, an ${\alpha}_{1b}$-adrenoceptor antagonist, but not by WB4101, an ${\alpha}_{1a}$-adrenoceptor antagonist. Also methoxamine inhibited the forskolin-, cAMP- or IBMX-stimulated $T_4$ release. These inhibition were reversed by PKC inhibitors, such as staurosporine and $H_7$. PMA, a PKC activator, completely inhibited the TSH-stimulated $T_4$ release, and its inhibition was reversed by staurosporine and $H_7$, but not by chelerythrine. R59022 (a diacylglycerol kinase inhibitor), like methoxamine, also inhibited the TSH-stimulated $T_4$ release, and its inhibition was also reversed by staurosporine. The present study suggests that methoxamine inhibition of $T_4$ release from mouse thyroid can be induced by activation of the ${\alpha}_{1b}$-adrenoceptors and that it is mediated through the ${\alpha}_1$-adrenoceptor-stimulated PKC formation.

• YAKHAK HOEJI
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• v.33 no.6
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• pp.333-338
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• 1989

It has been postulated that abnormal characteristics of central noradrenergic nervous system has been implicated in the development and maintenance of hypertension in several modes of experimental hypertension including spontaneously hypertensive rats (SHR). In the present study, we attempt to determine if abnormal characteristics of central noradrenergic nervous system in SHR is caused by genetic factors or hypertensive phenomena by evaluating the changes of central adrenoceptors after long-term treatment of clonidine. Animals were divided into three groups; (1) 14 week-old SHR; (2) age-matched normotensive Wistar rats (NW); (3) DOCA-Salt induced hypertensive rats (DS). Clonidine (100 ug/kg) or vehicle was injected intraperitonealy twice a day for 15 days. Changes of ${\alpha}_1-$ and ${\alpha}_2-receptor$ desities following clonidine treatment were determiend in frontal corte, medulla oblongata and hypothalamus using 3H-WB4101 and 3H-clonidine, respectively. Densities of ${\alpha}_1$ and ${\alpha}_2-receptors$ following clonidine treatment were not changed in frontal cortex and medulla oblongate of SHR as well as DS, but increased in frontal cortex of NW and decreased in medulla oblongata of NW. On the other hand, densities of ${\alpha}_1-receptors$ were increased and densities of ${\alpha}_2-receptors$ were not changed in hypothalamus of SHR but densities of ${\alpha}_1-$ and ${\alpha}_2-receptors$ were decreased in hypothalamus of DS as well as NW. These results suggest that such differences in frontal cortex and medulla oblongata of SHR may be results of hypertensive phenomena whereas those in hypothalamus may be relevant to genetic factors of SHR.