• Title/Summary/Keyword: CGRP

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EVIDENCE OF INTRAEPITHELIAL CGRP IMMUNOREACTIVE NERVE FIBERS DURING REEPITHELIALIZATION OF EXTRACTION WOUND OF RAT (흰쥐의 발치와 재상피화에 따른 상피내 CGRP 면역양성 신경섬유의 분포변화)

  • Byeon, Ki-Jeong;Kim, Chin-Soo
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.4
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    • pp.369-372
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    • 2000
  • The purpose of this study was to investigate the distribution pattern of CGRP immunoreactive nerve fibers in the healing mucosa of extracion wound. Maxillary 1st molars of rats were extracted. All extraction sites and adjacent tissues of 3 groups of rats(1-week, 2-week and 4-week groups) were removed en bloc and processed for immunostaining and were subjected to light microscopic examination. The results obtained were as follows; In 1-week group, there was no difference in the distribution pattern of CGRP immunoreactive nerve fiber between epithelial margin adjacent to extraction socket and normal gingival epithelium. In 2-week group, some CGRP-immunoreactive nerve fibers were seen in epithelial layer. In 4-week group, many intercellular CGRP immunoreactive nerve fibers were abundant in all layers of immature epithelium characterized by scab on the mucosa and thick keratinized cell layer with irregular surface. Intraepithelial CGRP immunoreactive nerve fibers were reduced to normal level in adjacent mature epithelium. These results suggest that density of CGRP immunoreactive nerve fibers are increased transiently in epithelium during reepithelialization process and CGRP released from these nerve fibers may play an important role in the reepithelialization in the wound healing.

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Normal Anxiety, Fear and Depression-related Behaviors in Mice Lacking ${\alpha}-Calcitonin$ Gene-Related Peptide

  • Lee, Jong-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.6 no.6
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    • pp.299-304
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    • 2002
  • Calcitonin gene-related peptide (CGRP) expressing neurons are distributed widely throughout the central and peripheral nervous systems. Due to its distribution and pharmacological studies, CGRP has been implicated to be involved in anxiety, fear and depression. In this study, ${\alpha}CGRP-knockout$ mice were used to assess the consequences of removing this neuropeptide to the mice behaviors. ${\alpha}CGRP-knockout$ mice performed equally as well as wild type mice in the light-dark transition test and in the elevated plus maze test of anxiety. ${\alpha}CGRP-null$ mice behaved similarly as wild-type mice in the Porsolt swim test of depression. They also exhibited normal learning and memory in the fear conditioning tasks. It is concluded that ${\alpha}CGRP$ is not essential for mice to be able to perform these tests, despite the presence of ${\alpha}CGRP$ in the relevant regions of the brain.

Changes of CGRP immunoreactivity in rat trigeminal ganglion neurons during tooth movement (백서 삼차신경절내 신경세포체의 치아이동에 따른 CGRP 면역염색성의 변화)

  • Park, Chyo-Sang;Park, Guk-Phil;Sung, Jae-Hyun
    • The korean journal of orthodontics
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    • v.27 no.4 s.63
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    • pp.607-621
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    • 1997
  • GRP was known as the modulator of Pain transmission in central nervous system and local effector to peripheral tissue causing vasodilation, increased blood flow, modulation of immune sysem, stimulation of endothelial cell proliferation, and stimulation of bone formation. Numerous study, therefore, were done to elucidate involvement of CGRP to tooth movement. To investgate the response of CGRP immunoreactive nerve cells according to cell size in trigeminal ganglion during tooth movement, immunohistochemical study was performed using rat. Experimental rats(9 weeks old, 210 gm) were divided as six groups(normal(n=6), 3 hour group(n=5), 12 hour group(n=4), 1 day group(n=5), 3 day group(n=5), 7 day group(n=5)), and were applied orthodontic force (approximately 30 gm) to upper right maxillary molar. After frozen sections of trigeminal ganglions were immunostained using rabbit antisera, the changes of CGRP immunoreactive cells in regard to cell size distribution(small cell(upto $20{\mu}m$), medium cell($20-35{\mu}m$), large cell(above $35{\mu}m$)) were observed. The results were as follows 1. The percentage of CGRP immunoreactive cells to all nerve cells in trigeminal ganglion was 33.0% in normal control group, was decreased to 24.5% in 1 day group, and was increased to 41.8% in 7 day group. 2. The percentage of small, medium, and large cells expressing CGRP immunoreactivity in normal trigeminal ganglion to all CGRP immunoreactive cells were 51.3%, 44.0%, 4.7%, respectively. 3. The percentage of small cells with CGRP immunoreactivity to all CGRP immunopositive cells was increased in 3 hour and 12 hour groups. 4. The percentage of medium cells with CGRP immunoreactivity was increaed in 3 day and 7 day groups. 5. The percentage of large cells with CGRP immunoreactivity was increaed in 7 day group. Conclusively, the small cells with CGRP immunoreactivity in trigeminal ganglion respond to orthodontic force during initial phase of tooth movement, and later the medium and large cells with CGRP immunoreactivity respond

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Pharmacological Action Mechanism(s) of Vasodilator Effect of Calcitonin Gene-related Peptide in Rat Basilar Arteries (흰쥐의 뇌 기저동맥에서 CGRP에 의한 혈관 이완반응의 기전에 대한 연구)

  • Rhim, Byung-Yong;Hong, Sun-Hwa;Kim, Chi-Dae;Lee, Won-Suk;Kim, Dong-Heon;Hong, Ki-Whan
    • The Korean Journal of Pharmacology
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    • v.32 no.1
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    • pp.39-49
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    • 1996
  • In the present study, we observed change in intracellular $Ca^{2+}$$([Ca^{2+}]_i)$ as measured with the fluorescent $Ca^{2+}-indicator$ fura-2 in association with force development of the rat basilar arteries during activation by$K^+$ depolarizing solution and U46619, a thromboxane analogue, in the absence and the presence of calcitonin-gent related peptide (CGRP). CGRP (30 and 100 nM) caused a concentration-dependent inhibition of U46619-induced contraction with decrease in $[Ca^{2+}]_i$, whereas it did not exert any effect on the $K^+$ (90 mM)-induced contraction and increase in $[Ca^{2+}]_i$, Further, $[Ca^{2+}]_i-force$ relationships were determined by plotting the ratio of $F_{340}/F_{380}$ $([Ca^{2+}]_i)$ as a function of the force induced by U46619, and the results were compared with those obtained in the presence of CGRP. The curves obtained in the presence of CGRP (30 and 100 nM) were significantly moved to downward without right shift of the curves suggesting that CGRP inhibited the U46619-induced contraction only by mediation of reduction in $[Ca^{2+}]_i$ with out any change in the sensitivity of contractile apparatus to $Ca^{2+}$. The CGRP-induced attenuation of $[Ca^{2+}]_i$ and force development was significantly inhibited under pretreatment with CGRP $(8{\sim}37)$ fragment (100 nM), a CGRP1 receptor antagonist. Both the reduced contraction and reduction in $[Ca^{2+}]_i$ caused by CGRP were fully reversed by pretreatment with charybdotoxin (100 nM) and iberiotoxin (100 nM), large conductance $Ca^{2+}-activated$ $K^+$ channel blockers, but not by apamin (300 nM), a small conductance $Ca^{2+}-activated$ $K^+$ channel blocker, and glibenclamide ( 1 ${\mu}M$), an ATP-sensitive $K^+$ channel blocker. In conclusion, it is suggested that the CGRP1 receptor, upon activation by CGRP, are coupled to opening of $Ca^{2+}-activated$ $K^+$ channel and cause to decrease in $[Ca^{2+}]_i$, thereby leading to vasodilation of the rat basilar artery. However, it is not defined that the mechanism underlying vasodilation whether the $K^+$ channel blockers, charybdotoxin and iberiotoxin directly block the CGRP receptors and that CGRP-evoked relaxation is dependent on the cyclic AMP or $K^+$ channel opening or both actions.

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EFFECT OF CAPSAICIN AND EUGENOL ON ICGRP (IMMUNOREACTIVE CALCITONIN GENE-RELATED PEPTIDE) RELEASE FROM RAT LUMBAR SPINAL CORD. (백서 척수에서 Capsaicin과 Eugenol이 iCGRP (immunoreactive calcitonin gene-related peptide) 분비 조절에 미치는 영향.)

  • 오원만;김원재;최남기;박상원;황인남;김선헌
    • Restorative Dentistry and Endodontics
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    • v.26 no.5
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    • pp.436-442
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    • 2001
  • Neuropeptide such as calcitonin gene-related peptide and substance P may mediate neurogenic inflammation, but little is known about the regulation of neuropeptide release from rat spinal cord. Eugenol has been reported to reduce odontogenic pain and is known to have a structure similar to capsaicin, a potent stimulant of certain nociceptors. This study was done to examine the effect of capsaicin and eugenol on immunoreactive calcitonin gene-related peptide (iCGRP) release from rat spinal cord and whether eugenol regulates capsaicin-sensitive release of iCCRP or it evokes capsaicin-sensitive release of iCGRP. The dor-sal half of rat lumbar spinal cord was chopped into 200$\mu$m slices. They were superfused (500$\mu$l/min) in vitro with an oxygenated Kreb's buffer. The EC$_{50}$ of capsaicin on iCGRP release was measured. Eugenol (600$\mu$M and 1.2mM) and vehicle (0.02% 2-hydroxyl-$\beta$-cyclodextrin) were administered prior to stimulation of rat lumbar spinal cord with capsaicin. The amount of iCGRP release from rat lumbar spinal cord was measured by radioimmunoassay. The results were as follows : 1. iCGRP release from rat lumbar spinal cord was dependent on concentration of capsaicin. The EC$_{50}$ of capsaicin on iCGRP release was 3$\mu$M. 2. In the vehicle treated group, capsaicin (3$\mu$M) evoked a 14-fold increase over basal iCGRP level. 3. Administration of 600$\mu$M and 1.2mM eugenol evoked a 2.2-fold increase and a 2.3-fold increase over basal iCGRP level respectively. 4. Administration of 600$\mu$M and 1.2mM eugenol increased capsaicin evoked release of iCGRP by more than 50%. These results indicate that eugenol evoke CGRP release from central nervous system and potentiate the pain-inducing action of capsaicin on it.

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REGULATION OF PULPAL MICROCIRCULATION BY CALCITONIN GENE-RELATED PEPTIDE (Calcitonin Gene Related Peptide에 의한 치수미세순환 조절)

  • Kim, Sung-Kyo;Kim, Young-Kyung;Jin, Myoung-Uk
    • Restorative Dentistry and Endodontics
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    • v.30 no.6
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    • pp.470-476
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    • 2005
  • The purpose of this Study was to invest)gate the function or calcitonin gene-related peptide (CGRP) in regulatory mechanism of pulpal microcirculation with the aim of elucidating neurogenic inflammation. Experiments were performed on twelve cats under general anesthesia. CGRP was administered through the femoral vein to see the systemic Influence and through the external carotid artery to see the local effect. Sympathetic nerve to the dental pulp was stimulated electrically and pulpal blood flow (PBF) was measured with a laser Doppler flowmeter on the canine teeth to the drug administration. The paired variables of control and experimental data were compared by paired t-test and differences with p < 0.05 were considered statistically significant. Systemic administration of CGRP $(0.3{\mu}g/ka)$ exerted decreases in systemic blood pressure and caused changes in PBF with an initial increase i311owed by decrease and a move marked second increase and decrease. Close intra-arterial (i.a.) injection of CCRP $(0.03{\mu}g/kg)$ resulted in slight PBF increase. The effect of CGRP resulted in no significant increase in PBF in the presence of $CGRP_{8-37}$. The electrical stimulation of the sympathetic nerve alone resulted in PBF decreases. The j.a. administration of CGRP following the electrical stimulation of the sympathetic nerve compensated the decreased PBF. Therefore, CGRP effectively blocked the sympathetic nerve stimulation-induced PBF decrease. Results of the present study have provided evidences that even though the local vasodilatory function of CGRP are weak, CCRP is effectively involved in blocking the vasoconstriction caused by sympathetic nerve stimulation in the feline dental pulp.

Localizations of substance P, CGRP and calcium binding proteins in Korean native goat duodenum (한국재래산양 십이지장의 장관신경계통에 분포하는 Substance P, CGRP 및 칼슘결합단백질 반응세포에 대한 면역조직화학적 연구)

  • Lee, In-se;Lee, Heungshik S.;Song, Seung-hoon;Yoon, Sung-tae;Hwang, In-koo;Kang, Tae-cheon;Won, Moo-ho;Seo, Je-hoon
    • Korean Journal of Veterinary Research
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    • v.39 no.3
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    • pp.435-447
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    • 1999
  • The localization of substance P(SP), calcitonin gene-related peptide(CGRP) and three calcium binding proteins, calbindin D-28k(CB), calretinin(CR) and parvalbumin(PA) was immunohistochemically examined in the myenteric and submucous plexuses of Korean native goat duodenum. In the neurons of myenteric and submucous plexuses of duodenum, immunoreactivities of SP, CGRP and CB were confirmed in both nerve cell bodies and fibers. In contrast, CR immunoreactivity was found only in nerve fibers of myenteric plexuses, while PA immunoreactivity was found only in nerve cell bodies of submucous plexuses. In the inner circular muscle layer, dense SP-like immunoreactive fibers were prominent but only a few CGRP-like immunoreactivities were observed. Most of SP- and CGRP-like immunoreactive neurons of both plexuses colocalized with CB. This result showed that SP and CGRP may have a important role for the movement of small intestine. The colocalizations of CB with SP or CGRP in myenteric and submucous plexuses suggest that CB may serve neuromodulatory role for SP- and CGRP-immunoreacted neurons on the movement of intestinal wall.

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Alpha-Calcitonin Gene-Related Peptide-Null Mice Shows Normal Responses to Various Noxious Stimuli

  • Lee, Jong-Ho;Emeson Ronald B.
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.6
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    • pp.323-327
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    • 2006
  • Despite the wealth of data concerning the roles of ${\alpha}-CGRP$ in nociceptive behaviors, ${\alpha}-CGRP-null$ mice showed no obvious phenotypic differences in nociceptive behaviors from wild type. The present studies specifically demonstrate that ${\alpha}-CGRP$ null mice showed no CGRP immunoreactivity from the spinal cord, implying that CGRPs in the mice spinal cord are mainly a-isoforms. However, the nociceptive behaviors of the null mice are not significantly different from the wild type mice in thermal nociceptive behaviors on hotplate, chemical nociception tests to intraplantar capsaicin or formalin injection, and visceral pain behaviors to intraperitoneal acetic acid or magnesium sulfate injections. These data suggest that ${\alpha}-CGRP$ is dispensable for nociceptive behaviors or that compensatory mechanisms may exist to overcome the absence of this peptide.

Changes in CGRP-immunoreactive Nerve Fibers during Expansion of Midpalatal Suture of the Rat (백서 정중구개봉합 확대후의 CGRP 면역반응 신경섬유의 변화)

  • Kim, Bo-Kyung;Park, Kuk-Pil;Kyung, Hee-Moon;Kwon, Oh-Won;Sung, Jae-Hyun
    • The korean journal of orthodontics
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    • v.29 no.1 s.72
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    • pp.73-81
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    • 1999
  • Midpalatal suture expansion is often used for patients haying narrow maxillary arch, cleft palate, respiratory handicap with narrow nasal cavity. CGRP has been known as a modulator of pain transmission in central nervous system and a local effector to peripheral tissue causing vasodilation, increase of blood flow, modulation of immune system, regulation of macrophagic function and stimulation of bone formation. To investigate changes of CGRP-immunoreactive nerve fibers in midpalatal suture during the expansion, immunohistochemical study was performed by using rats. Experimental rats (10 weeks, 250 gm) were divided into five groups (control, 1, 4, 7, 14 days group (each n=4) and applied orthodontic force (approximately 200gm) to upper anterior incisors. Frozen sections of midpalatal suture area were immunostained by using rabbit antisera. The results were as follows. ${\cdot}$ The CGRP-immunoreactive nerve fibers were hardly observed in control group. ${\cdot}$ In 1 day group, the CGRP-immunoreactive nerve fibers were more increased around the vessels than control group. ${\cdot}$ In 4 days group, the CGRP-immunoreactive nerve fibers were more increased than control group, but not more increased than 1 day group. Vascular diameter was more enlarged. ${\cdot}$ In 7 days group, especially, hematoxilin affinity of cells was remarkable and cells were arranged along the bone margin. The CGRP-immunoreactive nerve fibers were more reduced than 4 days group and vascular diameter was also reduced. ${\cdot}$ In 14 days group, the CGRP-immunoreactive nerve fibers were similar to those of 7 days group and the irregularity of bone margin was almost recoverd. In Conclusion, the CGRP-immunoreactive nerve fibers nay be related to initial neurogenic inflammatory reaction in expanding mid-palatal suture.

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EFFECT OF EUGENOL ON REGULATION OF iCGRP RELEASE FROM THE BOVINE DENTAL PULP (치수에서 Eugenol이 iCGRP(immunoreactive calcitonin gene-related peptide)의 분비 조절에 미치는 영향)

  • Oh, Won-Mann;Choi, Nam-Ki;Kim, Sun-Hun
    • Restorative Dentistry and Endodontics
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    • v.24 no.1
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    • pp.180-186
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    • 1999
  • Eugenol has been reported to reduce odontogenic pain and is known to have a structure similar to capsaicin, a potent stimulant of certain nociceptors. We have hypothesized that the analgesic effect of eugenol may be due, in part, to inhibition of capsaicin-sensitive nociceptors. To test this hypothesis, we evaluate whether eugenol inhibits capsaicin-sensitive release of immunoreactive calcitonin generated peptide(iCGRP) from bovine dental pulp. Freshly extracted bovine incisors were transported to the lab. on ice, Spilitted and pulp tissue was removed. The tissue was chopped into 200${\mu}m$ slices. Dental pulp was superfused(340 ${\mu}l/min$) in vitro with oxygenated Kreb's buffer. Eugenol and vehicle(0.02% 2-hydroxyl-${\beta}$-cyclodextrin) were administered prior to stimulation of pulp with capsaicin and iCGRP was measured by RIA. The results were as follows: 1. Administration of eugenol has no effect on basal release of iCGRP. 2. In the vehicle treated group, capsaicin evoked a 2.5-fold increase over basal iCGRP levels. 3. Administration of eugenol(600 ${\mu}M$) reduced capsaicin evoked release of iCGRP by more than 40%(153.4${\pm}$41.1% vs 258.9${\pm}$21.7%). 4. 2-hydroxylpropyl-${\beta}$-cyclodextrin of less than 0.02% is found to be an effective vehicle to dissolve eugenol without evoking iCGRP release from dental bovine pulp. These data indicate that eugenol inhibits pulpal capsaicin-sensitive fibers and suggest that intracanal medicament of eugenol may relieve pain, in part, by this mechanism.

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