• 제목/요약/키워드: Calcitonin gene related peptide

검색결과 57건 처리시간 0.021초

Expression of Nociceptin within Dura Mater in Response to Electrical Trigeminal Ganglion Stimulation in Rats

  • Kim, Jeong-Hee;Lee, Won-Suk
    • 대한의생명과학회지
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    • 제11권3호
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    • pp.375-382
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    • 2005
  • This study aimed to investigate whether nociceptin is implicated in the, trigeminovascular responses to electrical stimulation of trigeminal ganglion in rats. An open cranial window was prepared on the right parietal bone of male Sprague-Dawley rats. Trigeminovascular system was stimulated by electrical stimulation of trigeminal ganglion (ETS; 5ms, 5Hz, 3V). Neonatal capsaicin treatment was performed with subcutaneous administration of capsaicin (50mg/kg) within the first 24 hours after birth. Changes in regional cerebral blood flow were continuously measured through the cranial window by laser-Doppler flowmetry, and the expression of nociceptin-like immunoreactivity was determined by immunohistochemistry. ETS caused increases in regional blood flow of pial arteriole in a voltage-dependent manner. ETS markedly and voltage-dependently increased the expression of nociceptin-like immunoreactivity in dura mater ipsilateral rather than contralateral to ETS. The nociceptin-like immunoreactivity was markedly reduced by pretreatments with calcitonin gene-related peptide(8-37) ($CGRP_{8-37},\;a\;CGRP_1$ receptor antagonist), L-733060 (a $NK_1$ receptor antagonist), and $[Nphe^1]$ nociceptin(1-13)$NH_2$ (a selective and competitive nociceptin receptor antagonist) as well as by neonatal capsaicin treatment. These results suggest that the electrical stimulation of trigeminal ganglion causes prominent expression of nociceptin within dura mater, in which not only neuropeptides inducing substance P and CGRP but also nociceptin are implicated in the trigeminovascular responses to electrical trigeminal ganglion stimulation.

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한국재래산양 시각교차위핵 내 몇 가지 칼슘결합단백질과 신경전달물질의 분포에 관한 면역조직화학적 연구 (Immunohistochemical study on some calcium binding proteins and neurotransmitters in suprachiasmatic nucleus of the Korean native goat)

  • 송승훈;이흥식;이인세
    • 대한수의학회지
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    • 제41권2호
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    • pp.139-146
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    • 2001
  • This study was carry out to identify the distribution of calcium binding proteins; calbindin(CB), calretinin(CR) and parvalbumin(PA) in the suprachiasmatic nucleus(SCN) of the Korean native goat by immunohistochemical methods. The expression of substance P(SP), calcitonin gene-related peptide(CG-RP), neuropeptide Y(NPY), vasoactive intestinal polypeptide(VIP) and galanin(GAL) were also investigated. CR-immunoreactivity was found in both of the cell bodies and fibers in the SCN, which the CB-immunoreactivity was observed only in the fibers. The immunoreactivity for VIP was observed in both the cell bodies and fibers, but SP-, NPY, GAL-immunoreactivities were only found in the fibers. CGRP-immunoreactivity was not seen in cell body and fibers. These results suggest that VIP, SP, NPY and GAL play a neuromodulatory or/ and neurotransmitter roles in cooperation with CB and CR in SCN of the Korean native goat.

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Expression of neurotransmitter receptors in oral keratinocytes and their response to agonists

  • Choi, Eun Ji;Chang, Sung-Ho;Choi, Se-Young;Choi, Youngnim
    • International Journal of Oral Biology
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    • 제46권1호
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    • pp.39-44
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    • 2021
  • This study aimed to investigate whether neurotransmitter receptors in the nervous system were also expressed in oral keratinocytes. Expressions of various neurotransmitter receptor genes in immortalized mouse oral keratinocyte (IMOK) cells were examined by reverse transcriptase polymerase chain reaction. IMOK cells expressed calcitonin gene-related peptide (CGRP) receptor subunit genes Ramp1 and Ramp3 and glutamate receptor subunit genes Grina, Gria3, Grin1, Grin2a, and Grin2d. Moreover, IMOK cells expressed Adrb2 and Chrna5 that encode beta 2 adrenergic receptor and cholinergic receptor nicotinic alpha 5 for sympathetic and parasympathetic neurotransmitters, respectively. The expression of Bdkrb1 and Ptger4, which encode receptors for bradykinin and prostaglandin E2 involved in inflammatory responses, was also observed at low levels. Expressions of Ramp1 and Grina in the mouse gingival epithelium were also confirmed by immunohistochemistry. When the function of neurotransmitter receptors expressed on IMOK cells was tested by intracellular calcium response, CGRP, glutamate, and cholinergic receptors did not respond to their agonists, but the bradykinin receptor responded to bradykinin. Collectively, oral keratinocytes express several neurotransmitter receptors, suggesting the potential regulation of oral epithelial homeostasis by the nervous system.

수막 자극 증상으로 내원한 환자에서 두통과 관련된 신경 펩타이드에 대한 연구 (A study of neuropeptides related to headaches in children with meningeal irritation signs)

  • 서보길;유명환;심재원;심정연;정혜림;박문수;김덕수
    • Clinical and Experimental Pediatrics
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    • 제49권5호
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    • pp.533-538
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    • 2006
  • 목 적 : 무균성 수막염은 구토, 발열, 두통 등의 증상을 일으키며, 이때 발생하는 두통은 급격한 뇌압 상승이나 두개강 내 통증 연관 조직에 의한다고 한다. 하지만, 뇌압상승이 현저하지 않거나, 뇌척수액 소견이 정상인데도 두통을 호소하는 경우가 있어 수막염에서의 두통이 다른 경로를 통하여서도 발생하리라 생각된다. 이에 저자들은 두통 유발과 관련이 있는 SP와 CGRP의 뇌척수액 농도를 측정하여 무균성 수막염 및 수막자극증상에서의 역할 여부를 알아보고자 하였다. 방 법 : 2005년 6월부터 7월까지 수막자극증상이 있어 방문한 환자 75명을 대상으로 척수 천자를 시행하여 뇌압을 측정하고 얻은 뇌척수액 중 일부는 백혈구 수와 단백 및 당의 농도를 측정하고, 일부는 $-20^{\circ}C$로 보관하였다가 SP 면역분석 키트(R&D Systems, Inc., USA)와 CGRP 효소 면역분석 키트(Phoenix Pharmaceuticals, Inc., USA)를 이용하여 뇌척수액 농도를 측정하였다. 전체 환자를 뇌척수액의 백혈구 증가가 있었던 경우는 수막염 환자군으로, 정상 소견이었던 경우는 수막자극증상 환자군으로 구분하였고, 수막염 환자군에서 뇌압이 $18cmH_2O$ 이하인 경우는 정상 압력군으로, 초과인 경우는 압력 상승군으로 분류하였다. 통계 분석은 각 군에서의 비교를 위해서 Student's t-test, Pearson 상관분석법을 이용하였고 P값이 0.05 미만인 경우를 통계적 유의성이 있는 것으로 판단하였다. 결 과 : 수막염 환자군의 연령은 평균 7.5세였고, 척수천자시 압력은 $14.8{\pm}4.5cmH_2O$, 뇌척수액 백혈구 수는 $106.2{\pm}199.5/mm^3$, 단백농도는 $38.9{\pm}21.4mg/dL$, 혈액 백혈구 수는 $9,888.2{\pm}4,221.6/mm^3$이었다. 반면, 수막자극증상 환자군의 연령은 평균 6.9세였고, 척수천자시 압력은 $12.0{\pm}5.1cmH_2O$, 뇌척수액 백혈구 수는 $1.1{\pm}1.1/mm^3$, 단백농도는 $22.3{\pm}7.4mg/dL$, 혈액 백혈구 수는 $11,929.0{\pm}4,892.8/mm^3$이었다. 두 군에서의 SP와 CGRP의 농도는 수막염군에서 각각 $54.5{\pm}44.2pg/mL$, $18.8{\pm}10.5ng/mL$이었고, 수막자극증상군에서는 $47.1{\pm}38.2pg/mL$, $14.1{\pm}7.4ng/mL$이었다. 수막염과 수막자극증상 환자군에서의 SP 농도는 통계적으로 차이는 없었으나 CGRP 농도는 통계적으로 수막염군에서 높았다(P<0.05). 또한, 수막염 환자군에서 뇌압에 따라 비교했을 때 SP와 CGRP 농도가 정상 압력군에서 유의하게 높았다(P<0.05). 결 론 : 무균성 수막염이나 수막자극증에서 발생한 두통은 바이러스 감염으로 인한 SP와 CGRP의 활성화와 관련이 있으리라 판단된다. 하지만 본 연구에서는 정상 대조군 및 두통의 정도나 기간, 증상 회복 후 수치변화에 대한 자료가 포함되어 있지 않았고, 두통에 영향을 줄 수 있는 다른 케모카인이나 사이토카인이 고려되지 않았다. 따라서 향후에는 이런 제한점을 해결하고, 뇌내 혈관의 투과성과 관련이 있는 여러 물질에 대해서도 함께 연구가 수행되면 좋을 것으로 생각된다.

The Effect of GCSB-5 a New Herbal Medicine on Changes in Pain Behavior and Neuroglial Activation in a Rat Model of Lumbar Disc Herniation

  • Cho, Hee Kyung;Kim, So-Yeon;Choi, Mi Jung;Baek, Seung Ok;Kwak, Sang Gyu;Ahn, Sang Ho
    • Journal of Korean Neurosurgical Society
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    • 제59권2호
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    • pp.98-105
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    • 2016
  • Objective : Lumbar disc herniation can induce sciatica by mechanical compression and/or chemical irritation. The aim of this study was to compare the effects of GCSB-5 (Shinbaro$^{(R)}$) and NSAIDs on pain-related behavior and on the expressions of microglia, astrocytes, CGRP, TRPV1, IL-6, and CX3CL1 in a rat model of lumbar disc herniation. Methods : 112 male Sprague-Dawley rats underwent implantation of nucleus pulposus to a dorsal root ganglion (DRG). Rats were divided into five groups as follows; a saline group (the vehicle control group) (n=27), a 10 mg/kg aceclofenac group (the aceclofenac group) (n=22), and 100, 300 or 600 mg/kg GCSB-5 groups (the GCSB-5 100, 300, or 600 groups) (n=21 for each group). Rats were tested for mechanical allodynia at 3 days after surgery and at 1 day, 3 days, 7 days, 14 days, 21 days, 28 days, 35 days, 42 days, 49 days, and 56 days after treatment commencement. Immunohistochemical staining of microglia (Iba1), astrocytes (GFAP), CGRP, and TRPV1, and PCR for IL-6 and CX3CL1 were performed on spinal dorsal horns and DRGs at 56 days after medication commencement. Results : After 56 days of GCSB-5 300 administration, mechanical withdrawal thresholds were significantly increased (p<0.05), and immunohistochemical expressions of Iba1, GFAP, CGRP, and TRPV1 were reduced than other groups, but this difference was not statistically significant. Conclusion : These results indicate GCSB-5 reduces mechanical allodynia and downregulates neuroglial activity and the expressions of CGRP and TRPV1 in the spinal segments of a rat model of lumbar disc herniation.

Altered Cerebral Vasomotion with Decreased CGRP Level in Pial Arteries of Spontaneously Hypertensive Rats

  • Lee, Kwang-Ho;Choi, Jae-Moon;Hong, Ki-Whan
    • The Korean Journal of Physiology and Pharmacology
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    • 제2권5호
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    • pp.573-580
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    • 1998
  • The study aims to identify the mechanism (s) underlying the altered vasodilatory responses of the pial artery of spontaneously hypertensive rats (SHR) under a hypothesis that calcitonin gene-related peptide (CGRP) exerts a modulator role in the autoregulation of cerebral blood flow (CBF). The animals were divided into four groups: 1) Sprague-Dawley rats (SDR), 2) Wistar rats (WR), 3) SHR with high blood pressure $(BP{\ge}150\;mmHg),$ and 4) SHR with normotensive BP $({\le}150\;mmHg).$ The lower limit of CBF autoregulation in SHR shifted to a higher BP $(82.8{\pm}9.3\'mmHg,\;P<0.05)$ than that in SDR $(58.9{\pm}5.7\;mmHg)$. In SHR, whether the BP levels were high or normotensive, the vasodilator responses to a stepwise hypotension were significantly attenuated unlike with SDR and WR. When artificial cerebrospinal fluid (CSF) containing capsaicin $(3{\times}10^{-7}\;M)$ was suffused over the cortical surface, a transient increase in pial arterial diameter was observed in the SHR with high or normotensive BP. In contrast, SDR and WR showed a large increase in diameter, and the increase was sustained for over 10 minutes. In line with these results, the basal releases of CGRP-like immunoreactivity (CGRP-LI) in the isolated pial arteries from SHR with high and normotensive BP were $12.5{\pm}1.4\;and\;9.8{\pm}2.8\;fmole/mm^2/60\;min\;(P<0.05)$, while those from SDR and WR were $25.5{\pm}3.1\;and\;24.6{\pm}3.1\;fmole/mm^2/60\;min,$ respectively. The isolated basilar arteries showed similar results to those of the pial arteries in SHR. Thus, it is summarized that, in the SHR, the reduced autoregulatory vasodilator responses to stepwise hypotension and capsaicin may be, in part, ascribed to the decreased release of CGRP from the perivascular sensory nerve fibers of the pial arteries, and that altered vasomotor activity in SHR may not be related with the hypertensive tone.

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Influence of pain-relieving therapies on inflammation and the expression of proinflammatory neuropeptides after dental bleaching treatment

  • da Silva, Livia Maria Alves Valentim;Cintra, Luciano Tavares Angelo;de Oliveira Gallinari, Marjorie;Benetti, Francine;Rahal, Vanessa;Ervolino, Edilson;de Alcantara, Sibele;Briso, Andre Luiz Fraga
    • Restorative Dentistry and Endodontics
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    • 제45권2호
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    • pp.20.1-20.14
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    • 2020
  • Objectives: To minimize the tooth sensitivity caused by in-office bleaching, many dentists use non-steroidal anti-inflammatory drugs and topical desensitizing gels containing potassium nitrate and sodium fluoride. This study aimed to evaluate the influence of these substances on inflammation and the expression of substance P and calcitonin gene-related peptide in pulp nerve fibers. Materials and Methods: Seventy-two rats were divided into 6 groups as follows: GI, control; GII, only dental bleaching; GIII, only ibuprofen; GIV, ibuprofen administered 30 minutes before and after the bleaching treatment and every 12 hours until the analysis; GV, only topical application of a desensitizing agent; and GVI, topical application of a desensitizing agent before dental bleaching. Placebo gel was applied to the upper left jaw and the bleaching agent was applied to the upper right jaw in all groups. Subsequently, the groups were divided into 3 subgroups based on the time of analysis: 0, 24, and 48 hours after bleaching (n = 8). The rats were euthanized and the maxillae were processed and evaluated by histopathological and immunohistochemical analyses. The data were analyzed using the Kruskal-Wallis test, followed by the Dunn test (p < 0.05). Results: In the bleaching groups, the inflammatory process and expression of neuropeptides decreased over time. The animals in which a desensitizing agent was applied showed better results within 24 hours. Conclusions: The use of a desensitizing agent had positive effects on inflammation and pain-related neuropeptide expression, minimizing the painful effects of dental bleaching treatment.

Alterations in Meningeal Blood Flow by Stimulation of Trigeminovascular System in Rats

  • Kim, Byung-Soo;Choi, Chang-Hwa;Lee, Won-Suk
    • 대한의생명과학회지
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    • 제11권3호
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    • pp.365-373
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    • 2005
  • The aim of this study was to investigate the alterations in meningeal blood flow by stimulation of trigeminovascular system. An open cranial window was prepared on the right parietal bone of male Sprague-Dawley rats. Trigeminovascular system was stimulated by electrical stimulation of trigeminal ganglion (ETS), somatosensory (whisker) stimulation, or topical applications of capsaicin and neuropeptides including substance P and calcitonin gene-related peptide (CGRP). Neonatal capsaicin pretreatment was performed with subcutaneous administration of capsaicin (50 mg/kg) within the first 24 hours after birth. Changes in regional blood flow of dural artery (rDBF) and pial artery (rPBF) were continuously measured through the cranial window by laser-Doppler flowmetry. Both ETS and capsaicin caused a chain of alterations in rPBF and rDBF responses, i.e., an immediate transient decrease followed by rapid and marked increase in rPBF, which were significantly attenuated not only by pretreatments with L-733,060, a $NK_1$ receptor blocker, $CGRP_{8-37}$, a $CGRP_1$ receptor blocker, and 7-nitroindazole monosodium salt (7-NINA), a neuronal nitric oxide synthase inhibitor but also by neonatal capsaicin treatment. Exogenous neuropeptides including substance P and CGRP increased the meningeal blood flow, which was significantly attenuated not only by pretreatment with L-733,060 and $CGRP_{8-37}$, respectively, but also by pretreatment with 7-NINA. The rPBF response to whisker stimulation was significantly attenuated not only by trigeminovascular system injuries including nasociliary nerve denervation and neonatal capsaicin treatment but also by pretreatments with L-733,060, $CGRP_{8-37}$ and 7-NINA. These results suggest that the stimulation of trigeminovascular system causes prominent alterations in meningeal blood flow, and that neuropeptides as well as nitric oxide in the trigeminovascular system are importantly implicated in the regulation of meningeal blood flow.

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NITRIC OXIDE와 치수 (NITRIC OXIDE AND DENTAL PULP)

  • 김영경;김성교
    • Restorative Dentistry and Endodontics
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    • 제27권5호
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    • pp.543-551
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    • 2002
  • Nitric oxide (NO) is a small molecule (mol. wt. 30 Da) and oxidative free radical. It is uncharged and can therefore diffuse freely within and between cells across membrane. Such characteristics make it a biologically important messenger in physiologic processes such as neurotransmission and the control of vascular tone. NO is also highly toxic and is known to acts as a mediator of cytotoxicity during host defense. NO is synthesized by nitric oxide synthase (NOS) through L-arginine/nitric oxide pathway which is a dioxygenation process. NO synthesis involves several participants, three co-substrates, five electrons, five co-factors and two prosthetic groups. Under normal condition, low levels of NO are synthesized by type I and III NOS for a short period of time and mediates many physiologic processes. Under condition of oxidant stress, high levels of NO are synthesized by type II NOS and inhibits a variety of metabolic processes and can also cause direct damage to DNA. Such interaction result in cytostasis, energy depletion and ultimately cell death. NO has the potential to interact with a variety of intercellular targets producing diverse array of metabolic effects. It is known that NO is involved in hemodynamic regulation, neurogenic inflammation, re-innervation, management of dentin hypersensitivity on teeth. Under basal condition of pulpal blood flow, NO provides constant vasodilator tone acting against sympathetic vasoconstriction. Substance P, a well known vasodilator, was reported to be mediated partly by NO, while calcitonin-gene related peptide has provided no evidence of its relation with NO. This review describes the roles of NO in dental pulp in addition to the known general roles of it.

P2X and P2Y Receptors Mediate Contraction Induced by Electrical Field Stimulation in Feline Esophageal Smooth Muscle

  • Cho, Young-Rae;Jang, Hyeon-Soon;Kim, Won;Park, Sun-Young;Sohn, Uy-Dong
    • The Korean Journal of Physiology and Pharmacology
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    • 제14권5호
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    • pp.311-316
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    • 2010
  • It is well-known that electrical field stimulation (EFS)-induced contraction is mediated by a cholinergic mechanism and other neurotransmitters. NO, ATP, calcitonin gene-related peptide (CGRP), and substance P are released by EFS. To investigate the purinergic mechanism involved in the EFS-induced contraction, purinegic receptors antagonists were used. Suramine, a non-selective P2 receptor antagonist, reduced the contraction induced by EFS. NF023 ($10^{-7}{\sim}10^{-4}M$), a selective P2X antagonist, inhibited the contraction evoked by EFS. Reactive blue ($10^{-6}{\sim}10^{-4}M$), selective P2Y antagonist, also blocked the contraction in a dose-dependent manner. In addition, P2X agonist ${\alpha}$,${\beta}$-methylene 5'-adenosine triphosphate (${\alpha}{\beta}MeATP$, $10^{-7}{\sim}10^{-5}M$) potentiated EFS-induced contraction in a dose-dependent manner. P2Y agonist adenosine 5'-[${\beta}$-thio]diphosphate trilithium salt ($ADP{\beta}S$, $10^{-7}{\sim}10^{-5}M$) also potentiated EFS-induced contractions in a dose-dependent manner. Ecto-ATPase activator apyrase (5 and 10 U/ml) reduced EFS-induced contractions. Inversely, 6-N,$N$-diethyl-D-${\beta}$,${\gamma}$- dibromomethylene 5'-triphosphate triammonium (ARL 67156, $10^{-4}M$) increased EFS-induced contraction. These data suggest that endogenous ATP plays a role in EFS-induced contractions which are mediated through both P2X-receptors and P2Y-receptors stimulation in cat esophageal smooth muscle.