1.Effect of CGRP receptor antagonist CGRP8-37 on nociceptive response, NOS expression and NO content in the dorsal horn of spinal cord during formalin-induced inflammatory pain in rats.
Tong-nan LI ; Qing-jun LI ; Wen-bin LI ; Xiao-cai SUN ; Shu-qin LI
Chinese Journal of Applied Physiology 2004;20(3):291-295
AIMTo study the effect of CGRP receptor antagonist CGRP8-37 on nociceptive response and expression of nitric oxide synthase (NOS) and content of nitric oxide (NO) in the dorsal horn of the spinal cord of rats during formalin-induced inflammatory pain.
METHODSUsing formalin injection into right hind paw induced inflammatory pain. Counting the times of flinching reflex was used to observe the degree of spontaneous pain. NADPH-d histochemistry was used to observe the changes of NOS expression. The content of NO was observed by measuring the contents of nitrate/nitrite (NO3- / NO2-).
RESULTSspontaneous pain behavioral was elicited by formalin injection. The NOS expression and NO content significantly increased in the spinal cord at 24 h after formalin injection. Intrathecal injection of CGRP8-37 could significantly inhibit the response of spontaneous pain and the increases of NOS expression and NO content induced by formalin injection.
CONCLUSIONThe activation of CGRP receptors enhances NOS expression and NO production in the dorsal horn of the spinal cord during formalin-induced inflammatory pain.
Animals ; Calcitonin Gene-Related Peptide ; pharmacology ; Formaldehyde ; adverse effects ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Pain ; chemically induced ; metabolism ; Peptide Fragments ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Calcitonin Gene-Related Peptide ; antagonists & inhibitors ; Spinal Cord ; drug effects ; metabolism
2.Regulative effects of ovarian steroids on rat gastric motility and sensitivity.
Acta Physiologica Sinica 2006;58(3):275-280
Women often complain gut symptoms during pregnancy and the luteal phase of the menstrual cycle. To investigate the relationship between ovarian steroids and the abnormal gut motility and sensitivity, the expressions of cholecystokinin (CCK), calcitonin gene-related peptide (CGRP) and their receptors in stomach were studied in ovariectomized rats. Blood samples were collected for estradiol (E(2)), progesterone (P(4)), CCK and CGRP radioimmunoassay. Expression of CCK(A) receptor in fundus was assessed by Western blot and CGRP receptor was determined by (125)I-CGRP radioligand binding assay (RBA). The replacement therapy with estradiol benzoate (EB) could dose-dependently increase the plasma CCK level and the expression of gastric CCK(A) receptor (P<0.05 respectively). P(4) replacement therapy could stimulate the release of CGRP and increase the binding sites of CGRP receptors in stomach (P<0.05 respectively). The combined effect of EB and P(4) was to stimulate the release of CCK and CGRP, and to increase the expressions of gastric CCK(A) and CGRP receptors. These results indicate that EB could inhibit gastric emptying by increasing CCK secretion and CCK(A) receptor expression in ovariectomized rats. P(4) could increase gut sensitivity by up-regulating the release of CGRP and the activity of CGRP receptor. It could be deduced from these observations that CCK(A) and CGRP receptor antagonists could be used for female patients who suffer from gastrointestinal dysfunction closely related with the menstrual cycle, such as distension, satiety, bloating and abdominal pain.
Animals
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Calcitonin Gene-Related Peptide
;
blood
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Cholecystokinin
;
blood
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Estradiol
;
analogs & derivatives
;
pharmacology
;
physiology
;
Female
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Gastric Emptying
;
drug effects
;
physiology
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Ovariectomy
;
Progesterone
;
pharmacology
;
physiology
;
Rats
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Rats, Sprague-Dawley
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Receptors, Calcitonin Gene-Related Peptide
;
metabolism
;
Receptors, Cholecystokinin
;
metabolism
;
Stomach
;
metabolism
;
physiology
4.Adrenomedullin reduces intracellular calcium concentration in cultured hippocampal neurons.
Shu-Mei JI ; Jian-Mei XUE ; Chuan WANG ; Su-Wen SU ; Rui-Rong HE
Acta Physiologica Sinica 2005;57(3):340-345
The effects of adrenomedullin (ADM) on intracellular calcium concentration ([Ca(2+)](i)) were investigated in cultured hippocampal neurons. Changes in [Ca(2+)](i) were detected by laser scanning confocal microscopy using Fluo 3-AM as the calcium fluorescent probe. [Ca(2+)](i) was represented by relative fluorescent intensity. The results showed that: (1) ADM (0.01-1.0 micromol/L) decreased the resting [Ca(2+)](i) in a concentration-dependent manner. (2) Calcitonin gene-related peptide receptor antagonist CGRP(8-37) significantly inhibited the effects of ADM. (3) ADM significantly reduced the increase in [Ca(2+)](i) induced by high K(+). (4) ADM markedly inhibited the inositol 1,4,5-trisphosphate (IP(3))-induced increase in [Ca(2+)](i), while did not influence ryanodine-evoked increase in [Ca(2+)](i). These results suggest that ADM reduces [Ca(2+)](i) in cultured hippocampal neurons through suppressing Ca(2+) release from IP(3)-sensitive stores. Although ADM does not alter resting Ca(2+) influx, it significantly suppresses Ca(2+) influx activated by high K(+). These effects may be partly mediated by CGRP receptors. ADM in the CNS may act as a cytoprotective factor in ischemic/hypoxic conditions.
Adrenomedullin
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Animals
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Animals, Newborn
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Calcitonin Gene-Related Peptide
;
metabolism
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Calcium
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metabolism
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Cells, Cultured
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Embryo, Mammalian
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Hippocampus
;
cytology
;
metabolism
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Inositol 1,4,5-Trisphosphate
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antagonists & inhibitors
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Neurons
;
cytology
;
metabolism
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Peptides
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pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Calcitonin Gene-Related Peptide
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antagonists & inhibitors
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metabolism
5.Regulatory mechanisms and therapeutic potential of microglial inhibitors in neuropathic pain and morphine tolerance.
Er-Rong DU ; Rong-Ping FAN ; Li-Lou RONG ; Zhen XIE ; Chang-Shui XU
Journal of Zhejiang University. Science. B 2020;21(3):204-217
Microglia are important cells involved in the regulation of neuropathic pain (NPP) and morphine tolerance. Information on their plasticity and polarity has been elucidated after determining their physiological structure, but there is still much to learn about the role of this type of cell in NPP and morphine tolerance. Microglia mediate multiple functions in health and disease by controlling damage in the central nervous system (CNS) and endogenous immune responses to disease. Microglial activation can result in altered opioid system activity, and NPP is characterized by resistance to morphine. Here we investigate the regulatory mechanisms of microglia and review the potential of microglial inhibitors for modulating NPP and morphine tolerance. Targeted inhibition of glial activation is a clinically promising approach to the treatment of NPP and the prevention of morphine tolerance. Finally, we suggest directions for future research on microglial inhibitors.
Humans
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Calcitonin Gene-Related Peptide/antagonists & inhibitors*
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Drug Tolerance
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Hypoglycemic Agents/pharmacology*
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Microglia/physiology*
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MicroRNAs/physiology*
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Minocycline/pharmacology*
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Morphine/pharmacology*
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Neuralgia/etiology*
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Plant Extracts/pharmacology*
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Signal Transduction/physiology*
6.Vasodilating effect of capsaicin on rat mesenteric artery and its mechanism.
Qiang CHEN ; Huanhuan ZHU ; Yuanyuan ZHANG ; Yuan ZHANG ; Lihong WANG ; Liangrong ZHENG
Journal of Zhejiang University. Medical sciences 2013;42(2):177-183
OBJECTIVETo investigate the vasodilating effect of capsaicin (CAP) on rat mesenteric artery and its mechanism.
METHODSThe third branch of the superior mesenteric artery in male Sprague-Dawley rat (250-350 g) was excised, the periadventitial fat and connective tissue were removed and the mesenteric artery was dissected into 2 mm rings. Each ring was placed in a 5 ml organ bath of DMT 610M system and the tension was recorded.
RESULTSCAP (10(-9)-10(-5) mol/L) relaxed endothelium-intact and endothelium-denuded mesenteric artery pre-constricted by phenylephrine (10(-5) mol/L), and the vasodilation in endothelium-intact mesenteric artery was stronger than that in endothelium-denuded one. Pretreatment with either L-NAME (3 X10(-4) mol/L), an inhibitor of nitric oxide synthase(NOS), or CGRP8-37 (2 X 10(-6) mol/L), an antagonist of calcitonin gene-related peptide (CGRP), for 30 min significantly attenuated the relaxation of endothelium-intact mesenteric artery induced by CAP. CGRP (10(-10)-3 X10(-8) mol/L) relaxed endothelium-intact and endothelium-denuded mesenteric artery pre-constricted by phenylephrine, and the vasodilation in endothelium-intact mesenteric artery was stronger than that in endothelium-denuded one. Substance P did not relax the mesenteric artery pre-constricted by phenylephrine.
CONCLUSIONCAP has partial endothelium-dependent relaxation effect on rat mesenteric artery, which may be mediated by activating the endothelial NOS-NO pathway. The endothelium-independent relaxation in rat mesenteric artery induced by CAP may be mediated by CGRP.
Animals ; Calcitonin Gene-Related Peptide ; metabolism ; Capsaicin ; pharmacology ; In Vitro Techniques ; Male ; Mesenteric Arteries ; drug effects ; physiology ; Peptide Fragments ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vasodilation ; drug effects
7.CGRP inhibits proliferation, activation and cytokine secretion of group 2 innate lymphoid cells (ILC2) in peripheral blood from patients with allergic rhinitis.
Hedi ZHUO ; Xueping QI ; Nuowen XU ; Yanjie WANG ; Yunfang AN ; Jinmei XUE ; Changqing ZHAO
Chinese Journal of Cellular and Molecular Immunology 2023;39(12):1094-1099
Objective To investigate the effect of calcitonin gene-related peptide (CGRP) on the regulation of group 2 innate lymphoid cells (ILC2) in the peripheral blood of patients with allergic rhinitis (AR). Methods Peripheral blood mononuclear cells (PBMCs) were extracted from normal healthy individuals and AR patients, then stimulated with CGRP, interleukin 33 (IL-33) and CGRP combined with IL-33 for 3 days, with blank stimulus as control. The percentage of ILC2 in the four groups was measured by flow cytometry. After being sorted, ILC2 was given to CGRP, IL-33 and CGRP combined with IL-33 stimulation for 3 days, with blank stimulus as control. The percentage of IL-5 and IL-13 positive cells in ILC2 was detected by flow cytometry, and the levels of IL-5 and IL-13 in ILC2 supernatant were measured by ELISA. Results The percentage of ILC2 in the peripheral blood of AR patients was significantly higher than that of the control group. The levels of IL-5+ILC2 and IL-13+ILC2 were significantly increased by IL-33 single stimulation after culturing PBMCs. After adding IL-33 combined with CGRP stimulation, the levels of IL-5+ILC2 and IL-13+ILC2 in PBMCs were significantly reduced; after CGRP single stimulation, the levels of IL-5+ILC2 and IL-13+ILC2 in PBMCs were further decreased. After ILC2 was sorted and cultured, the levels of IL-5+ILC2 and IL-13+ILC2 showed significant increase after IL-33 single stimulation. The levels of IL-5+ILC2 and IL-13+ILC2 were decreased by IL-33 and CGRP co-stimulation, and they were further reduced after CGRP single stimulation. Compared to IL-33 single stimulation, IL-5 and IL-13 levels dropped significantly due to the IL-33 and CGRP co-stimulation. The levels of IL-5 and IL-13 were further reduced by CGRP single stimulation. Conclusion CGRP inhibits the proliferation and activation of peripheral blood ILC2 in AR and exert anti-inflammatory effects in AR.
Humans
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Calcitonin Gene-Related Peptide/pharmacology*
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Leukocytes, Mononuclear
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Immunity, Innate
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Interleukin-33/pharmacology*
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Interleukin-13
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Lymphocytes
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Interleukin-5/pharmacology*
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Rhinitis, Allergic
;
Cell Proliferation
8.Involvement of the receptor component protein in the regulation of vascular peroxidase-1 expression induced by calcitonin gene-related peptide and angiotensin II in vascular smooth muscle cell.
Yan-Mei LIU ; Hong-Yan PENG ; Feng GUO ; Hai-Yan QUAN ; Jing-Fei LUO ; Xu-Ping QIN
Acta Physiologica Sinica 2015;67(2):193-200
Angiotensin II (Ang II) and calcitonin gene-related peptide (CGRP) play important roles in vascular injury and protection. In order to determine the role of CGRP receptor component protein (RCP) in signal transduction whereby CGRP and Ang II mediate the expression of vascular peroxidase-1 (VPO1) in vascular smooth muscle cell (VSMC), mouse derived A10 vascular smooth muscle cell line (A10VSMC) was cultured with CGRP or/and Ang II in vitro. RCP-specific small interference RNA (siRNA-RCP) was used to silence oligonucleotide sequence. Western blot and RT-PCR were used to determine the protein and mRNA expressions of RCP and VPO1, respectively. The results showed that the expressions of RCP and VPO1 were increased in the presence of CGRP or Ang II in the quiescent A10VSMC. But the protein expressions of RCP and VPO1 induced by Ang II were decreased by pretreatment of CGRP (P < 0.05). The expressions of VPO1 were decreased in all the groups treated with siRNA-RCP, compared with those of wide-type counterparts. Meanwhile, the expression of VPO1 was significantly induced by CGRP but not Ang II in the siRNA-RCP treated A10VSMCs. Ang II in combination with CGRP increased the protein expression of VPO1 in the siRNA-RCP-transfected cells, compared with Ang II alone, and this effect could be abolished by catalase. The results suggest that RCP may play an important role in the integration of signal transduction whereby CGRP and Ang II receptors jointly regulate VPO1 expression in VSMC.
Angiotensin II
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pharmacology
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Animals
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Calcitonin Gene-Related Peptide
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pharmacology
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Mice
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Muscle, Smooth, Vascular
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cytology
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Myocytes, Smooth Muscle
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metabolism
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Peroxidases
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metabolism
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RNA, Small Interfering
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Signal Transduction
9.Roles of calcitonin gene-related peptide family in pain and opioid tolerance.
Acta Physiologica Sinica 2013;65(3):347-354
The calcitonin gene-related peptide (CGRP) family mainly includes CGRPα, CGRPβ, adrenomedullin, calcitonin and amylin. The members of CGRP family and their receptors are widely distributed in the central and peripheral nervous systems. Studies show that members of CGRP family such as CGRP and adrenomedullin play important roles in the transmission of nociceptive information. At spinal level, CGRP promotes the transmission of nociceptive information, spinal morphine tolerance, migraine, inflammatory pain and neuropathic pain. At superspinal level, CGRP suppresses the transmission of nociceptive information. Adrenomedullin is a pain-related neuropeptide which has recently been demonstrated. It facilitates the transmission of nociceptive information and is involved in the development and maintenance of opioid tolerance. The involvement of amylin and calcitonin in pain is not clear yet.
Adrenomedullin
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physiology
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Analgesics, Opioid
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pharmacology
;
Animals
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Calcitonin Gene-Related Peptide
;
physiology
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Drug Tolerance
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Humans
;
Islet Amyloid Polypeptide
;
physiology
;
Nociception
;
Pain
;
physiopathology
10.Advances in the endocrine factors affecting the development of gubernaculum testis.
National Journal of Andrology 2006;12(5):446-449
The testicular gubernaculum plays an important role in testicular descent and development. Its differentiation and development are affected by many factors. Androgens, calcitonin gene-related peptide (CGRP), insulin-like factor 3 (INSL3), Müllerian inhibiting substance (MIS), epidermal growth factor (EGF) and environmental estrogens (EEs) are involved in gubernacular development. The effect of CGRP, INSL3 and especially EEs on genital system has been attracted more attention.
Animals
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Calcitonin Gene-Related Peptide
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physiology
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Estrogens
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pharmacology
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Humans
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Insulin
;
physiology
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Male
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Mice
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Proteins
;
physiology
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Rats
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Testis
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drug effects
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embryology
;
physiology