• The Journal of Korean Physical Therapy
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• 제15권4호
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• pp.442-454
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• 2003

The aim of this study was to demonstrate the effects of silver spike point (SSP) low frequency electrical stimulation on plasma vasoactive intestinal polypeptide (VIP) activities measured by radioimmunoassay from volunteer and the effects of VIP on pain substance-induced contraction investigated by isometric tension methode in animal. The current of 3 Hz continue type, but not 100 Hz continue type, of SSP low frequency electrical stimulation significantly increased in plasma VIP from normal volunteer. The pain substance, such as norepinephrine, serotonin, and prostaglandin $F2{\alpha}$, increased vascular smooth muscle contraction, respectively. These responses were inhibited by VIP applied cumulatively (1 nM - $1\;{\mu}M$), but not serotonin-induced contraction. In addition, serotonin, and prostaglandin $F2{\alpha}$ induced uterine smooth muscle contraction from rat. However, these responses were inhibited by VIP ($1\;{\mu}M$), only serotonin-induced contraction. These results suggest that the VIP regulates pain substance in part and that the SSP low frequency electrical stimulation, specifically current of 3 Hz continue type, significantly increases plasma VIP from volunteer.

• Molecules and Cells
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• 제21권3호
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• pp.337-342
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• 2006

Interstitial cells of Cajal (ICCs) are pacemaker cells that activate the periodic spontaneous depolarization (pacemaker potentials) responsible for the production of slow waves in gastrointestinal smooth muscle. The effects of vasoactive intestinal polypeptide (VIP) on the pacemaker potentials in cultured ICCs from murine small intestine were investigated by whole-cell patch-clamp techniques. Addition of VIP (50 nM-$1{\mu}M$) decreased the amplitude of pacemaker potentials and depolarized resting membrane potentials. To examine the type of receptors involved in ICC, we examined the effects of the $VIP_1$ agonist and found that it had no effect on pacemaker potentials. Pretreatment with $VIP_1$ antagonist ($1{\mu}M$) for 10 min also did not block the VIP (50 nM)-induced effects. On the other hand exposure to 1H-(1,2,4)oxadiazolo(4,3-A)quinoxalin-1-one (ODQ, $100{\mu}M$), an inhibitor of guanylate cyclase, prevented VIP inhibition of pacemaker potentials. Similarly KT-5823 ($1{\mu}M$) or RP-8-CPT-cGMPS ($10{\mu}M$), inhibitors of protein kinase G (PKG) blocked the effect of VIP (50 nM) on pacemaker potentials as did N-nitro-L-arginine (L-NA, $100{\mu}M$), a non-selective nitric oxide synthase (NOS) inhibitor. These results imply that the inhibition of pacemaker activity by VIP depends on the NO-cGMP-PKG pathway.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.443-454
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• 1998

The present study was attempted to investigate the effect of vasoactive intestinal polypeptide (VIP) on secretion of catecholamines (CA) and to establish whether there is the existence of a noncholinergic mechanism in adrenomedullary CA secretion from the isolated perfused rat adrenal gland. The perfusion into an adrenal vein of VIP $(3{\times}10^{-6}\;M)$ for 5 min or the injection of acetylcholine (ACh, $5.32{\times}10^{-3}\;M$) resulted in great increases in CA secretion. Tachyphylaxis to releasing effect of CA evoked by VIP was not observed by the repeated perfusion. The net increase in adrenal CA secretion evoked by VIP still remained unaffected in the presence of atropine or chlorisondamine. However, the CA release in response to ACh was greatly inhibited by the pretreatment with atropine or chlorisondamine. The releasing effects of CA evoked by either VIP or ACh were depressed by pretreatment with nicardipine, TMB-8, and the perfusion of $Ca^{2+}$-free medium. Moreover, VIP- as well as ACh-evoked CA secretory responses were markedly inhibited under the presence of $(Lys^1,\;Pro^{2.5},\;Arg^{3.4},\;Tyr^6)-VIP$ or naloxone. CA secretory responses induced by ACh and high $K^+\;(5.6{\times}10^{-2}\;M)$ were potentiated by infusion of VIP $(3{\times}10^{-6}M\;for\;5\;min)$. Taken together, these experimental results indicate that VIP causes CA release in a fashion of calcium ion -dependence, suggesting strongly that there exists a noncholinergic mechanism that may be involved in the regulation of adrenomedullary CA secretion through VIP receptors in the rat adrenal gland, and that VIP may be the noncholinergic excitatory secretagogue present in the chromaffin cells.

• 대한수의학회지
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• 제35권3호
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• pp.447-458
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• 1995

This study was carried out to characterize nonadrenergic, noncholinergic(NANC) relaxation of porcine retractor penis(PRP) muscle induced by electrical field stimulation(EFS) and to investigate the actions of niric oxide(NO) and vasoactive intestinal polypeptide(VIP) as candidates for NANC neurotransmitters. Biphasic relaxations of PRP muscle were induced by EFS to NANC nerve. Rapid-phase relaxation was observed at low frequency(0.5-16Hz) and slow-phase relaxation followed during high frequency(8-60Hz). Both relaxations were frequency-dependent and TTX($1{\times}10^{-6}M$)-sensitive. L-NAME($2{\times}10^{-5}M$) inhibited the rapid-phase relaxation, but not the slow-phase relaxation. The inhibition of the rapid-phase relaxation with L-NAME was reversed by L-arginine ($1{\times}10^{-3}M$) but not by D-arginine($1{\times}10^{-3}M$). Methylene blue($4{\times}10^{-5}M$) reduced the rapid-phase relaxation. Exogenous No(ExoNO, $1{\times}10^{-5}-1{\times}10^{-4}M$) induced dose-dependent relaxations of PRP muscle. Oxyhemoglobin($5{\times}1^{-5}M$) blocked the relaxation induced by ExoNO and inhibited EFS-induced relaxation. Hydroquinone($1{\times}10^{-4}M$) also abolished the relaxation induced by ExoNO, but did not affect EFS-induced relaxation. L-NAME resistant slow-phase relaxation to EFS was inhibited by ${\alpha}$-chymotrypsin(2.5 U/ml). Both methylene blue($4{\times}10^{-5}M$) and Nethylmaleimide($1{\times}10^{-4}M$) reduced the slow-phase relaxation by EFS. [4-Cl-D-$Phe^6$, $Leu^{17}$]-VIP($3{\times}10^{-6}M$) inhibited the slow-phase relaxation by EFS. External applications of VIP ($1{\times}10^{-7}M$) caused relaxations that were simillar to the L-NAME resistant slow-phase relaxations induced by EFS, and relaxant effects of exogenous VIP were blocked by ${\alpha}$-chymotrypsin(2.5 U/ml).

• BMB Reports
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• 제47권7호
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• pp.369-375
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• 2014

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic bioactive peptide that was first isolated from an ovine hypothalamus in 1989. PACAP belongs to the secretin/glucagon/vasoactive intestinal polypeptide (VIP) superfamily. PACAP is widely distributed in the central and peripheral nervous systems and acts as a neurotransmitter, neuromodulator, and neurotrophic factor via three major receptors (PAC1, VPAC1, and VPAC2). Recent studies have shown a neuroprotective role of PACAP using in vitro and in vivo models. In this review, we briefly summarize the current findings on the neurotrophic and neuroprotective effects of PACAP in different brain injury models, such as cerebral ischemia, Parkinson's disease (PD), and Alzheimer's disease (AD). This review will provide information for the future development of therapeutic strategies in treatment of these neurodegenerative diseases.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.217-217
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• 1996

The putative role of vasoactive intestinal polypeptide (VIP) as non-adrenergic non-cholinergic (NANC) neurotransmitter has been studied in rabbit corpus cavernosum. In the presence of atropine and guanethidine the short and prolonged electrical field stimulation (EFS, 2～16 ㎐) induced a frequency-dependent relaxation which was abolished by tetrodotoxin (0.3 ${\mu}$M), a nerve conductance blocker. The neurogenic relaxant reponses were not affected in the presence of VIP-inactivating peptidase, ${\alpha}$-chymotrypsin (2 units/$m\ell$), whereas VIP-induced relaxation were completely abolished. Inhibition of nitric oxide synthase by N$\^$G/-nitro-L-arginine (10～100 ${\mu}$M) caused concentration-dependent inhibition to the neurogenic relaxant responses and at 100 ${\mu}$M the relaxations were virtually abolished. In contrast NO (3～30 ${\mu}$M) and VIP (0.001～l ${\mu}$M)-induced relaxation were unaffected. The inhibitory effect of L-NNA was reversed in the presence of L-arginine (5 mM), the precursor of the NO biosynthesis. Hemog1obin (20～60 ${\mu}$M), sequestering NO in the extracellular space, abolished the NO-evoked relaxation and also caused a concentration-dependent inhibition to the neurogenic relaxation. These observation indicate that NANC relaxation induced by prolonged EFS of rabbit corpus cavernosum is also mediated mainly by nitric oxide as same as that of short EFS, and suggest that VIP is not involved in NANC relaxation of rabbit corpus cavernosum and NO would not be produced by VIP in this tissue.

• 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.

• Archives of Pharmacal Research
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• 제18권2호
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• pp.121-128
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• 1995

The role of nitric oxide (NO) in non-adrenegic non-cholinergic (NANC) neurotransmission was studied on circular muscle strips of the dorsal part of the fuinea-pig gastric fundus. In the presence of atropine and guanethidine, a low frequency-dependent relaxsations which were not affected by adrenergic and cholinergic blockage but abolished by tetrodotoxin. $N^G$-nitro-L-arginine (L-NNA), a stereospecific inhibitor of NO-biosynthesis, inhibited the relaxations induced by electrical stiumulations but not the relaxations to exogenous nitric oxide. The effect of L-NNA was prevented by L-arginine, the precursor of the NO biosynthesis but not by its enantiomer, D-arginine. Exgenous administration of No caused concentration -dependent relaxations which showed a similarity to those obtained with electrical simultaion. Hemoglobin, a NOscavenger, abolished the NO-induced relaxations and also markedly reduced those induced by electrical simultaion. The inhibitory effect os hemoglobin was similar to that of L-NNA. Application of ATP caused weak relaxations compared with those to electrical stimultaion, which were unaffected by L-NNA. Exogenously applied vasoactive intestinal polypeptide (VIP) induced concentration-dependent relaxation which was not affected by L-NNA. These results suggest that NO is produced and released mainly as a neurotransmitter from enteric neurons during NANC relaxation induced by low frequencies and short trains of electrical simulation and has a main role in NANC neurotransmission at relaxation induced by these electrical simultaions in the guinea-pig gastric fundus.

• Animal cells and systems
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• 제4권1호
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• pp.95-100
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• 2000

The regional distribution and relative frequencies of endocrine cells were studied immunogistochemically (PAP methods) in the alimentary tract of the tree frog, Hyla areorea japonica, using specific antisera against serotonin, somatostatin, bovine Sp-1/chromogranin (BCG), cholecystokinin (CCK)-8, vasoactive intestinal polypeptide (VIP), gastrin, bombesin, secretin and pancreatic polypeptide (PP). Six kinds of endocrine cells were identified in this study, These immunoreactive cells were located in the gastric glands of stomach regions and in the basal portion of the epithelium of the intestinal tract or esophagus with variable frequencies. They were spherical or spindle-shaped. Serotonin-immunoreactive cells were observed in the whole alimentary tract including the esophagus. Somatostatin-immunoreactive cells were also detected throughout the alimentary tract except the rectum. CCK-8-immunoreactive cells were observed from the pylorus to ileum. Vip-immunoreactive cells were restricted to the rectum. Bombesin-immunoreactive cells were restricted to the fundic gastric regions and gastrin-immunoreactive cells were restricted to the pylorus. However, no BCG-, secretin and PP-immunoreactive cells were demonstrated in this study. In conclusion, the regional distribution and relative frequency of the endocrine cells in the alimentary tract of the tree frog were similar to other anuran species, but some differences which may be caused by feeding habits and species specification were also observed.

• 대한수의학회지
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• 제41권4호
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• pp.477-484
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• 2001

붕어 (Carassius auratus Linnaeus)의 장에 존재하는 소화관 내분비세포의 부위별 분포 및 출현빈도를 포유류의 peptide에 대한 10종류의 항혈청을 사용하여 면역조직화학적 방법으로 관찰하였다. 붕어의 장은 근위부에서부터 원위부까지 5 등분했으며 (Segments I~V), 대부분의 면역반응세포들은 상피부분의 상피세포들 사이 공간에서 관찰되었으며, 장 내강까지 신장되어 있는 긴 세포질돌기를 함유한 방추형의 개방형 세포 (open type cell)들이 주로 관찰되었으나, 세포질돌기 없이 원형 또는 타원형의 형태를 나타내는 폐쇄형 세포 (close type cell)들 역시 소수 관찰되었다. 본 실험에서는 somatostatin, cholecystokinin (CCK)-8 및 pancreatic polypeptide (PP) 면역반응세포들이 관찰되었으나, serotonin, glucagon, chromogranin A, secretin, vasoactive intestinal peptide (VIP), substance P 및 bombesin 면역반응세포들은 관찰되지 않았다. 한편 somatostatin 면역반응세포들은 장의 가장 근위부인 Segment I에 국한되어 극소수 관찰되었으며, CCK-8 면역반응세포들은 장의 근위부인 Segment I과 II에서 소수 또는 극소수의 빈도로 관찰되었다. PP 면역반응세포들 역시 장의 근위부에서 중간 부위인 Segment I에서부터 III에 걸쳐 중등도 또는 극소수의 빈도로 출현하였다. 이상에서 붕어 위 내분비세포들의 부위별 분포 및 출현 빈도는 다른 위가 없는 경골어류 (stomachless teleost)에서의 보고들과 유사하였으나, 독특한 분포를 나타내는 면역반응세포들 역시 관찰되었다.