• Molecules and Cells
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• 제37권11호
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• pp.804-811
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• 2014

The protease-activated receptor (PAR)-2 is highly expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although several mechanisms have been suggested to explain PAR-2-induced hypotension, the precise mechanism remains to be elucidated. To investigate this possibility, we investigated the effects of PAR-2 activation on N-type $Ca^{2+}$ currents ($I_{Ca-N}$) in isolated neurons of the celiac ganglion (CG), which is involved in the sympathetic regulation of mesenteric artery vascular tone. PAR-2 agonists irreversibly diminished voltage-gated $Ca^{2+}$ currents ($I_{Ca}$), measured using the patch-clamp method, in rat CG neurons, whereas thrombin had little effect on $I_{Ca}$. This PAR-2-induced inhibition was almost completely prevented by ${\omega}$-CgTx, a potent N-type $Ca^{2+}$ channel blocker, suggesting the involvement of N-type $Ca^{2+}$ channels in PAR-2-induced inhibition. In addition, PAR-2 agonists inhibited $I_{Ca-N}$ in a voltage-independent manner in rat CG neurons. Moreover, PAR-2 agonists reduced action potential (AP) firing frequency as measured using the current-clamp method in rat CG neurons. This inhibition of AP firing induced by PAR-2 agonists was almost completely prevented by ${\omega}$-CgTx, indicating that PAR-2 activation may regulate the membrane excitability of peripheral sympathetic neurons through modulation of N-type $Ca^{2+}$ channels. In conclusion, the present findings demonstrate that the activation of PAR-2 suppresses peripheral sympathetic outflow by modulating N-type $Ca^{2+}$ channel activity, which appears to be involved in PAR-2-induced hypotension, in peripheral sympathetic nerve terminals.

• The Korean Journal of Physiology and Pharmacology
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• 제18권6호
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• pp.489-495
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• 2014

Protease-activated receptor (PAR)-2 is expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although some reports have suggested involvement of a neurogenic mechanism in PAR-2-induced hypotension, the accurate mechanism remains to be elucidated. To examine this possibility, we investigated the effect of PAR-2 activation on smooth muscle contraction evoked by electrical field stimulation (EFS) in the superior mesenteric artery. In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA). However, thrombin, a potent PAR-1 agonist, had no effect on EFS-evoked contraction. Additionally, ${\omega}$-conotoxin GVIA (CgTx), a selective N-type $Ca^{2+}$ channel ($I_{Ca-N}$) blocker, significantly inhibited EFS-evoked contraction, and this blockade almost completely occluded the suppression of EFS-evoked contraction by PAR-2 agonists. Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by ${\omega}$-CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of $I_{Ca-N}$ which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension.

• The Korean Journal of Physiology and Pharmacology
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• 제14권5호
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• pp.273-278
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• 2010

Tropical inhabitants are able to tolerate heat through permanent residence in hot and often humid tropical climates. The goal of this study was to clarify the peripheral mechanisms involved in thermal sweating pre and post exposure (heat-acclimatization over 10 days) by studying the sweating responses to acetylcholine (ACh), a primary neurotransmitter of sudomotor activity, in healthy subjects (n=12). Ten percent ACh was administered on the inner forearm skin for iontophoresis. Quantitative sudomotor axon reflex testing, after iontophoresis (2 mA for 5 min) with ACH, was performed to determine directly activated (DIR) and axon reflex-mediated (AXR) sweating during ACh iontophoresis. The sweat rate, activated sweat gland density, sweat gland output per single gland activated, as well as oral and skin temperature changes were measured. The post exposure activity had a short onset time (p<0.01), higher active sweat rate [(AXR (p<0.001) and DIR (p<0.001)], higher sweat output per gland (p<0.001) and higher transepidermal water loss (p<0.001) compared to the pre-exposure measurements. The activated sweat rate in the sudomotor activity increased the output for post-exposure compared to the pre-exposure measurements. The results suggested that post-exposure activity showed a higher active sweat gland output due to the combination of a higher AXR (DIR) sweat rate and a shorter onset time. Therefore, higher sudomotor responses to ACh receptors indicate accelerated sympathetic nerve responsiveness to ACh sensitivity by exposure to environmental conditions.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.287-295
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• 1998

Diazepam is known to have cardiovascular depressive effects through a combined action on benzodiazepinergic receptor and the GABA receptor-chloride ion channel complex. Moreover, it is known that barbiturates also have some cardiovascular regulatory effects mediated by the central GABAergic system. Therefore, this study was undertaken to delineate the regulatory actions and interactions of these systems by measuring the responses of the cardiovascular system and renal nerve activity to muscimol, diazepam and pentobarbital, administered intracerebroventricularly in rabbits. When muscimol $(0.03{\sim}0.3\;{\mu}\;g/kg)$, diazepam $(10{\sim}100\;{\mu}\;g/kg)$ and pentobarbital $(1{\sim}10\;{\mu}\;g/kg)$ were injected into the lateral ventricle of the rabbit brain, there were similar dose-dependent decreases in blood pressure (BP) and renal nerve activity (RNA). The relative potency of the three drugs in decreasing BP and RNA was muscimol ＞ pentobarbital ＞ diazepam. Muscimol and pentobarbital also decreased the heart rate in a dose-dependent manner; however, diazepam produced a trivial, dose-independent decrease in heart rate. Diazepam $(30\;{\mu}g/kg)$ augmented the effect of muscimol $(0.1\;{\mu}g/kg)$ in decreasing blood pressure and renal nerve activity, but pentobarbital $(3\;{\mu}g/kg)$ did not. Bicuculline $(0.5\;{\mu}g/kg)$, a GABAergic receptor blocker, significantly attenuated the effect of muscimol in decreasing BP and RNA, either alone or with diazepam, and that of pentobarbital in decreasing BP and RNA, either alone or with muscimol. We inferred that the central benzodiazepinergic and barbiturate systems help regulate peripheral cardiovascular function by modulating the GABAergic system, which adjusts the output of the vasomotor center and hence controls peripheral sympathetic tone. Benzodiazepines more readily modulate the GABAergic system than barbiturates.

• The Korean Journal of Physiology
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• 제20권1호
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• pp.1-7
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• 1986

췌장의 분비기능에 대한 자율신경계의 영향은 이미 잘 알려져있다. 그러나 자율신경계를 거쳐 위장계의 기능을 조절하는 중추신경계가 췌장의 분비기능에 미치는 영향은 아직 알려져 있지 않다. 그러므로 본 연구에서는 자율신경계의 작용을 통합하는 기능을 지닌 것으로 여겨지는 중뇌의 망상체가 췌장의 분비기능에 미치는 영향을 알아보고자 하였다. 24시간 절식시킨 흰쥐 22마리를 urethane으로 마취하고 췌장액을 채취하기 위하여 췌장관에 가는 관을 삽입하였으며 담즙은 공장으로 우회시켰다. 또한 위액이 십이지장으로 넘어오지 못하도록 위-십이지장 연결부를 결찰하였다. 뇌정위 고정장치를 이용하여 중뇌의 망상체에 양측성으로 전극을 삽입하였다. 10분간에 흘러나오는 췌장액의 분비량이 일정하게 되었을때 전기자극 발생장치에서 얻어지는 1.3 V, 40Hz, 2msec의 전기자극을 이미 삽입한 전극을 통하여 망상체에 10분간 가하였다. 이어서 경부에서 미주신경을 양측성으로 절단하거나 또는 ${\beta}-adrenoceptor$의 길항체인 propranolol을 0.1mg/kg되게 경정맥을 통하여 주입하였으며, 10분이 경과한 다음에 망상체의 전기자극을 반복하였다. 이상의 실험이 끝나면 10% formalinedyddor을 심장을 통하여 관류하여 뇌를 고정하였으며 후에 전극의 위치를 조직학적으로 확인하였다. 채취한 췌장액으로부터 단백질 분비량과 amylase 분비량을 측정하였다. 중뇌의 망상체를 전기자극하면 췌장액의 분비량$({\mu}l/10min)$, 단백질분비량$({\mu}g/10min)$ 그리고 amylase분비량(U/10min) 모두가 유의하게 증가하였다. 이러한 망상체의 자극효과는 미주신경의 절단에 의하여서는 아무런 영향을 받지 않았으나 propranolol의 투여에 의하여서는 완전히 억제되었다. 또한 미주신경의 절단과 propranolol의 투여에 의하여 췌장의 분비기능이 유의하게 감소함을 관찰하겠다. 이상의 결과로 미루어보아 마취된 흰쥐에서 중뇌의 망상체는 췌장의 분비기능에 촉진적인 영향을 미치며, 이러한 영향은 교감신경계의 ${\beta}-receptor$를 거쳐 일어나는 것으로 생각된다.