Calcitonin gene-related peptide (CGRP) play a key role in some physiological and pathological progresses. The latest studies indicate that CGRP might involve in some disease progress and has a close relation with wound healing. It is significant to further investigate and then apply it to clinical diagnosis and therapy as well as forensic pathology.
Animals ; Calcitonin Gene-Related Peptide/physiology* ; Forensic Medicine ; Humans ; Receptors, Calcitonin Gene-Related Peptide/physiology* ; Wound Healing

Animals ; Calcitonin Gene-Related Peptide ; physiology ; Heart ; physiology ; Male ; Physical Exertion ; physiology ; Rats ; Rats, Sprague-Dawley

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 ; Calcitonin Gene-Related Peptide ; blood ; Cholecystokinin ; blood ; Estradiol ; analogs & derivatives ; pharmacology ; physiology ; Female ; Gastric Emptying ; drug effects ; physiology ; Ovariectomy ; Progesterone ; pharmacology ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Calcitonin Gene-Related Peptide ; metabolism ; Receptors, Cholecystokinin ; metabolism ; Stomach ; metabolism ; physiology

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 ; Calcitonin Gene-Related Peptide ; physiology ; Estrogens ; pharmacology ; Humans ; Insulin ; physiology ; Male ; Mice ; Proteins ; physiology ; Rats ; Testis ; drug effects ; embryology ; physiology

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

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 ; physiology ; Analgesics, Opioid ; pharmacology ; Animals ; Calcitonin Gene-Related Peptide ; physiology ; Drug Tolerance ; Humans ; Islet Amyloid Polypeptide ; physiology ; Nociception ; Pain ; physiopathology

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 ; Calcitonin Gene-Related Peptide/antagonists & inhibitors* ; Drug Tolerance ; Hypoglycemic Agents/pharmacology* ; Microglia/physiology* ; MicroRNAs/physiology* ; Minocycline/pharmacology* ; Morphine/pharmacology* ; Neuralgia/etiology* ; Plant Extracts/pharmacology* ; Signal Transduction/physiology*

The purpose of this study was to investigate the effects of calcitonin gene-related peptide (CGRP) on the repolarization process in isolated guinea-pig atrial cells and to determine the contribution of K(+) channels to the CGRP-induced changes in action potential using conventional microelectrode method at the physiological temperature. We found that: (1) CGRP (16 nmol/L) antagonized the influences of potassium channel blockers, 4-AP and BaCl2, on action potential; (2) CGRP (16 nmol/L) increased the amplitude and maximum depolarizing velocity of slow action potential and shortened the conducting time in guinea pig atrial myocardium at extracellular K(+) concentration of 18.5 mmol/L; (3) CGRP (16 nmol/L) alleviated triggered activity induced by superfusion with solution containing CsCl and no potassium ion; and (4) the effects of CGRP on the configuration of action potential were temperature-dependent. At the temperature of 36.5+/-0.5 degrees C, CGRP (5, 16, and 50 nmol/L) increased the amplitude of the action potential and shortened APD(20), APD(50) and APD(90). The CGRP effects on APD(20) and APD(50) were dose-dependent and reversible. On the contrary, CGRP prolonged APD(20), APD(50) and APD(90) at the temperature of 25.5+/-2.1 degrees C. The present study suggests that CGRP possesses multiple effects on various ionic channels. Among them the effects on potassium currents are major determinants in the changes in action potential induced by CGRP under physiological temperature. It is necessary to further study the influences of CGRP on different types of potassium channels.
Action Potentials ; drug effects ; physiology ; Animals ; Body Temperature ; Calcitonin Gene-Related Peptide ; pharmacology ; Cells, Cultured ; Female ; Guinea Pigs ; Heart Atria ; cytology ; drug effects ; Male ; Potassium Channels ; physiology

AIMRats cardiovascular expression of CGRPmRNA surveyed after an eight-week swimming training, and molecular mechanism of exercise-induced adaptation were studied.

METHODS24 purebred male SD rats were divided randomly into three groups (n = 8): control (CR), exhaust (ER), train (TR). After swimming training left ventricular muscle and main artery arch were extracted, we inspected the expression of CGRPmRNA by RT-PCR.

RESULTS(1) Comparing with the control group, once exhausting exercise had no significant effect on cardiovascular expression of CGRPmRNA. (2) Comparing with the control group, long-term aerobic swimming training upregulated significantly cardiac expression of CGRPmRNA.

CONCLUSIONLong-term aerobic training induced benign cardiac adaptation in molecular level. Long-term aerobic swimming training had no significant effect on vascular expression of CGRPmRNA.

Animals ; Calcitonin Gene-Related Peptide ; genetics ; metabolism ; Cardiovascular System ; metabolism ; Male ; Physical Conditioning, Animal ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Swimming ; physiology

OBJECTIVEPrevious studies have clarified that calcitonin gene-related peptide (CGRP) can promote the biologi- cal activity of osteoblasts. To further reveal the role of CGRP in bone repair, we studied its influence on osteogenic differentia- tion of mouse bone marrow stromal cells (BMSCs) and initially explored the effect of the Hippo signaling pathway with this process.

METHODSBMSCs were induced to osteogenic differentiate osteoblasts by different concentrations of CGRP for a screening of the optimal concentration. CGRP was added in BMSCs, then the activity of alkaline phosphatase (ALP) and the number of mineralized nodules were examined by specific ALP kits after 48 hours and alizarin red staining fluid after 7 days, respectively. The protein expression of p-Mst1/2 was measured by Western blot. Verteporfin was used to block the downstream Yap signaling. The mRNA expression of collagen type I (Col I) and runt-related transcription factor 2 (Runx2) were detected by reverse transcription-polymerase chain reaction.

RESULTSCompared to the blank group, different concentrations of CGRP (10⁻⁹, 10⁻⁸, 10⁻⁷ mol · L⁻¹), especially 10⁻⁸ mol · L⁻¹, significantly increased the ALP activity of BMSCs (P < 0.05). Alizarin red staining also showed more mineralized nodules in 10⁻⁸ mol · L⁻¹ group. The expression of p-Mst1/2 increased in the CGRP group (P < 0.05). Verteporfin treatment effectively decreased the mRNA expression of Runx2 and Col I (P < 0.05).

CONCLUSIONThe Hippo signaling pathway plays a role in CGRP-induced osteogenic differentiation in mouse BMSCs.

Alkaline Phosphatase ; Animals ; Calcitonin ; genetics ; metabolism ; Calcitonin Gene-Related Peptide ; metabolism ; Cell Differentiation ; Cells, Cultured ; Collagen Type I ; Core Binding Factor Alpha 1 Subunit ; Mesenchymal Stromal Cells ; physiology ; Mice ; Osteoblasts ; Osteogenesis ; physiology ; Signal Transduction