• Molecules and Cells
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• v.37 no.11
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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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• v.18 no.6
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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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• v.14 no.5
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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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• v.2 no.3
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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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• v.20 no.1
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• pp.1-7
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• 1986

It has been well documented that the peripheral autonomic nervous system plays an important role in exocrine pancreatic secretion. However, the role of the central nervous system in pancreatic function is still obscure even though the central nervous system has been known to control gastrointestinal functions through the autonomic nervous system. Since the reticular formation in the mesencephalone seems to integrate the autonomic function, the present study was undertaken to investigate a possible influence of the reticular formation upon the exocrine pancreatic secretion. Twenty·two albino rats fasted for 24 hours were anesthetized by intraperitoneal injection of urethane in a dose of 1 g/kg, The pancreatic duct was cannulated to collect pancreatic juice and bile juice was diverted to the jejunum. The gastroduodenal junction was ligated to Prevent passage of gastic juice into the duodenum. A pair of electrodes were bilaterally inserted in the reticualr formation of the mesencephalone with aid of a stereotaxic apparatus. When the volume of pancreatic juice secreted for 10 min became constant, the reticular formation was electrically stimulated for 10 min. Parameters of the electical stimulation was 1.3V, 40 Hz and 2 msec. When the pancreatic secretion returned to the level before the electrical stimulation, cervical vagotomy (11 rats) or administration of propranolol (11 rats) in a dose of 0.1 mg/kg through the jugular vein was carried out. Ten minutes after the treatment, the electrical stimulation of the reticular formation was repeated. The brain was fixed by perfusion of 10% formaline solution through the heart, and then placement of the electrode tip was examined histologically. Protein concentration and amylase activity in samples of Pancreatic secretion were measured. The electrical stimulation of the reticular formation significantly increased in volume $({\mu}l/10\;min)$, Protein output $({\mu}g/10\;min)$ and amylase output (U/10 min) in the pancreatic secretion. The stimulatroy effects were not affected by the cervical vagotomy but completely abolished by propranolol. Meantime, it was also observed that both vagotomy and propranolol significantly reduced the pancreatic secretory function. These results indicate that the reticular formation in the mesencephalone may exert a stimulatory effect upon the Pancreatic secretory function not through the vagus nerve but through the sympathetic pathway in anesthetized rats.