Abstract:
:In previous studies, we have shown that calcitonin gene-related peptide (CGRP) acutely inhibits 45Ca2+ uptake in osteoblastic UMR106 cells, and we have proposed that ATP-sensitive potassium (K(ATP)) channels are involved in mediating this action of CGRP. To directly test this proposed mechanism, we have now examined the effects of CGRP on both membrane potential (Em) and K+ mobilization in UMR106 cells, using specific fluorometric dye assays. CGRP (0.01-100 nM) induced membrane hyperpolarization in a dose-dependent manner, with a half maximal effect (ED50) at approximately 0.2 nM and a maximal effect at 100 nM. Both pinacidil (Pina; a K(ATP) channel opener) and forskolin (FSK) induced similar membrane hyperpolarization, but the actions of these three agents could be easily distinguished: both CGRP and Pina actions were well antagonized by glibenclamide (Glib; a selective K(ATP) channel blocker), whereas FSK action was strongly attenuated only by tetraethylammonium (a K(Ca) channel blocker) or compound H-89 (an inhibitor of cAMP-dependent protein kinases). Cells pretreated with Pina no longer responded to CGRP, but they could still respond to FSK; furthermore, pretreatment with FSK failed to block successive treatment with either CGRP or Pina. In parallel with observed changes in Em, CGRP (0.01-100 nM) decreased intracellular K+ concentrations ([K+]i) in a dose-dependent manner, with an ED50 identical to that obtained for alterations in Em. This action of CGRP was sensitive to Glib and had only slight sensitivity to tetraethylammonium; this CGRP effect was mimicked by Pina but not by FSK. Interestingly, CGRP significantly elicited changes in cell shape by a Glib-sensitive mechanism that included notable decreases in cross-sectional cytoplasmic area. These observations strongly support our proposal that CGRP primarily stimulates K+ efflux via activation of K(ATP) channels and thereby induces membrane hyperpolarization in UMR106 cells. Furthermore, our data also suggest that this cascade of initial cellular events may result in rapid changes in cell morphology and decreases in cellular area of the type that are thought to act as triggers for proliferation and/or differentiation in many cellular phenotypes.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Kawase T,Burns DMdoi
10.1210/endo.139.8.6151subject
Has Abstractpub_date
1998-08-01 00:00:00pages
3492-502issue
8eissn
0013-7227issn
1945-7170journal_volume
139pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::The FOXO family of forkhead transcription factors stimulates the transcription of target genes involved in many fundamental cell processes, including cell survival, cell cycle progression, DNA repair, and insulin sensitivity. The activity of FOXO proteins is principally regulated by activation of protein kinase B (PKB...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2003-0481
更新日期:2003-12-01 00:00:00
abstract::The population of LHRH neurons was examined in young and middle-aged female rats at two different time points associated with the LH surge on proestrus. More immunopositive LHRH neurons were detected in the brains of young but not middle-aged females killed on the evening of proestrus (1830-2030 h) compared with those...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.134.1.8275960
更新日期:1994-01-01 00:00:00
abstract::The steady state levels of the prodynorphin-derived opioid peptides, dynorphin A, dynorphin B, and alpha-neo-endorphin, have been extensively studied in the magnocellular/posterior pituitary system of the rat. To determine whether the rat system serves as a general model for prodynorphin processing in the mammalian po...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-120-1-230
更新日期:1987-01-01 00:00:00
abstract::This study was conducted to determine the feasibility of using replication-defective adenovirus vectors to express receptors for LH. Two vectors were constructed, one that directs the expression of wild-type human LH receptor (LHr; AdRSVLHrwt) and another that directs the expression of the constitutively activated D57...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.142.6.8017
更新日期:2001-06-01 00:00:00
abstract::Childhood obesity increases the risk of adult obesity and diabetes, suggesting that early overnutrition permanently programs altered energy and glucose homeostasis. In the present studies, we used a mouse model to investigate whether early overnutrition increases susceptibility to obesity and insulin resistance in res...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2009-1295
更新日期:2010-04-01 00:00:00
abstract::Glucagon-like peptide 1 (7-36)amide (GLP-1) is an insulinotropic intestinal peptide hormone with a potential role as antidiabetogenic therapeutic agent. It mediates a potentiation of glucose-induced insulin secretion, by activation of adenylate cyclase and subsequent elevation of cytosolic free calcium, [Ca2+]cyt. We ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.9.6947
更新日期:1999-09-01 00:00:00
abstract::Products of the Stannius corpuscles (SC) of rainbow trout were tested in an established PTH bioassay involving bone resorption in embryonic mouse calvaria. Aqueous extracts from Stannius corpuscles (SC-homogenate) showed a bone-resorbing activity comparable to PTH in 24-h cultures of calvaria, indicated by a dose-depe...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-119-5-2249
更新日期:1986-11-01 00:00:00
abstract::Glial cell line-derived neurotrophic factor (GDNF) is expressed in many neuronal and non-neuronal tissues during development as well as in adult animals. GDNF signaling is mediated through a two-component system consisting of the so called GDNF receptor-alfa (GFRalpha1) which binds to GDNF. Thereafter this complex bin...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.141.5.7548
更新日期:2000-05-01 00:00:00
abstract::In vitro addition of rat insulin (200, 400 or 800 muU/ml) to collagenase-isolated pancreatic islets of adult rats diminished glucose (3 mg/ml)-induced insulin release which was correlated with a decrease of the ratio of total NADPH/NADP and inhibition of glucose oxidation via the pentose phosphate shunt (PPS). NADH an...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-99-6-1469
更新日期:1976-12-01 00:00:00
abstract::To further characterize the effect of TSH administration on thyroid iodothyronine monodeiodinating activity, we have evaluated the in vitro conversion of T4 to T3 (outer ring deiodination) and T3 to 3,3'-diiodothyronine (T2; inner ring deiodination) by mouse thyroid, liver, and kidney homogenates, comparing tissues fr...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-116-3-901
更新日期:1985-03-01 00:00:00
abstract::Androgens play a critical role in the development and progression of prostate cancer (PCa), and androgen deprivation therapy via surgical or medical castration is front-line therapy for patients with advanced PCa. However, intratumoral testosterone levels are elevated in metastases from patients with castration-resist...
journal_title:Endocrinology
pub_type: 杂志文章,评审
doi:10.1210/en.2014-1337
更新日期:2014-11-01 00:00:00
abstract::Selective serotonin-reuptake inhibitors (SSRIs) antagonize the serotonin (5-hydroxytryptamine) transporter (5-HTT), and are frequently prescribed to children and adolescents to treat depression. However, recent findings of functional serotonergic pathways in bone cells and preliminary clinical evidence demonstrating d...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2004-1259
更新日期:2005-02-01 00:00:00
abstract::The induction of long-term responses in the uterus following estrogen treatment is discussed, with special reference to DNA synthesis. Immature female rats injected daily with estradiol-17beta or estriol (0.01 to 1 mug) or a combination of the two steroids for one, two or three consecutive days were sacrificed at inte...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-99-6-1501
更新日期:1976-12-01 00:00:00
abstract::Hypophysectomized female rats which received renal grafts of anterior pituitary (AP) or weight-matched intact controls were sampled under urethane anesthesia. Plasma growth hormone (GH) in sequential samples from each rat was measured by radioimmunoassay to determine the effect of exogenous thyrotropin-releasing hormo...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-98-3-807
更新日期:1976-03-01 00:00:00
abstract::The ability of cultured midpregnancy mouse ovarian cells to synthesize progesterone de novo and from oxogenous pregnenolone has been assessed. The conversion of pregnenolone to progesterone is almost completely blocked by cyanoketone, a known inhibitor of delta5,3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity,...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-99-3-800
更新日期:1976-09-01 00:00:00
abstract::Decidualization, the process by which fibroblastic human endometrial stromal cells (HESC) differentiate into secretory decidual cells, is a critical event during the establishment of pregnancy. It is dependent on the steroid hormone progesterone acting through the nuclear progesterone receptor (PR). Previously, we ide...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endocr/bqz021
更新日期:2020-01-01 00:00:00
abstract::A variety of chronic stress paradigms have been shown to increase basal activity in the hypothalamic-pituitary-adrenocortical axis, resulting in hypercorticoidism. Despite this, chronically stressed rats typically exhibit facilitated ACTH responses to acute novel stress, suggesting that the activity of some central ne...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.133.6.8243290
更新日期:1993-12-01 00:00:00
abstract::Endotoxin has been shown to stimulate GH secretion in human and sheep. However, changes in hypothalamic neurohormones involved in the GH regulation by endotoxin have never been studied in vivo. In sheep it is possible to collect hypophysial portal blood (HPB) and quantify GH-releasing hormone (GHRH) and somatostatin (...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.139.6.6072
更新日期:1998-06-01 00:00:00
abstract::Previous studies have established the presence of an extrahypothalamic GnRH in a variety of tissues. GnRH receptor is known to be present in the placenta, which produces and secretes the decapeptide from the very early stages of placentation. We hypothesized that GnRH may play a role in the preimplantation development...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.8.6899
更新日期:1999-08-01 00:00:00
abstract::The role of GH during the ovine estrous cycle is unknown. In this study, pituitary GH mRNA and peripheral serum GH levels were measured in ewes representing the major phases of the estrous cycle. There was a significant rise (P less than 0.05) in both GH mRNA and serum GH concentrations during the follicular phase of ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-125-3-1474
更新日期:1989-09-01 00:00:00
abstract::Synthetic selective thyroid hormone (TH) receptor (TR) modulators (STRM) exhibit beneficial effects on dyslipidemias in animals and humans and reduce obesity, fatty liver, and insulin resistance in preclinical animal models. STRM differ from native TH in preferential binding to the TRβ subtype vs. TRα, increased uptak...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2011-1325
更新日期:2012-01-01 00:00:00
abstract::The purpose of this study was to examine the relative roles of FSH and LH in stimulating testicular inhibin secretion in the male rhesus monkey. Recombinant human (rh) FSH and rhCG were used as the gonadotropic stimuli, and juvenile rhesus monkeys, in which the endocrine activity of the pituitary-testicular axis was b...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.4.5058
更新日期:1997-04-01 00:00:00
abstract::Uterine ornithine decarboxylase (ODC) activity is reported to increase after estrogen administration to fetal, neonatal, immature, and adult rats, suggesting that it may be a useful marker in studies of the development of estrogen responsiveness. Standard conditions were validated for enzyme assay of uterine cytosols ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-113-5-1826
更新日期:1983-11-01 00:00:00
abstract::In cultured rat pituitary cells, increases in the cytosolic calcium concentration ([Ca2+]i) and LH release are induced by activation of GnRH receptors as well as by nonreceptor-mediated stimuli. Treatment of pituitary cells with the myosin light chain kinase (MLCK) inhibitor, wortmannin, attenuated GnRH-induced LH rel...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.4.5078
更新日期:1997-04-01 00:00:00
abstract::The estrogen receptor (ER) mixed agonists tamoxifen and raloxifene have been shown to protect against bone loss in ovariectomized rats. However, the mechanism by which these compounds manifest their activity in bone is unknown. We have used a series of in vitro screens to select for compounds that are mechanistically ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.9.5358
更新日期:1997-09-01 00:00:00
abstract::Is it well known that LHRH agonists can inhibit testicular functions by gonadal desensitization secondary to endogenous LH release and that a direct action at the gonadal level has also been demonstrated. Since an excess of anti-LH serum can be used, as an alternative to hypophysectomy, to neutralize the influence of ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-110-2-524
更新日期:1982-02-01 00:00:00
abstract::GH has physiological functions in many tissues, but the cellular targets for direct effects of GH remain ill defined in complex tissues such as the growth plate in which the contribution of direct vs. indirect actions of GH remains controversial. The Janus kinase (Jak)-signal transducer and activator of transcription ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2008-0985
更新日期:2009-08-01 00:00:00
abstract::Two corticotropin-releasing factor 2 receptor (CRF2R)-selective peptides have been recently described, urocortin II (also known as stresscopin-related peptide) and urocortin III (stresscopin). We have used urocortin II to evaluate the effects of activation of the CRF2R on skeletal muscle-related physiological processe...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2003-0271
更新日期:2003-11-01 00:00:00
abstract::In different types of mammalian cells, insulin has been shown to promote the release of an inositol phosphate glycan (InsP-glycan) through the hydrolysis of a glycosyl-phosphatidylinositol (glycosyl-PtdIns). This InsP-glycan, which has been demonstrated to be taken up by intact cells, may mediate some of the biologica...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.134.3.8119190
更新日期:1994-03-01 00:00:00
abstract::The level of fructose 2,6-bisphosphate (F2,6P2), a potent stimulator of 6-phosphofructo-1-kinase and inhibitor of fructose 1,6-bisphosphatase, was measured in three different muscle types (tensor fascia latae, biceps femoris, and soleus) and in the liver of normal and diabetic rats. The mean (+/- SEM) content of F2,6P...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-118-1-108
更新日期:1986-01-01 00:00:00