Serotonin Receptor Agonists That Increase Cyclic AMP Positively Regulate IGF-I in Mouse Mandibular Mesenchymal Cells

Lambert, H. Wayne; Jm, Lauder

doi:10.1159/000017372

Cited by 27 publications

(34 citation statements)

References 37 publications

(35 reference statements)

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“…It is well known that 5-HT 4 receptor activation stimulates cyclic AMP (cAMP) production. 16) Finally, in addition to these stimulants, foskolin, a cAMP activator, was used to directly increase intracellular cAMP concentration without combined with any receptor. The DC 4 segments were also more sensitive to it.…”

Section: Discussionmentioning

confidence: 99%

Segmental Heterogeneity of Epithelial Ion Transport Induced by Stimulants in Rat Distal Colon

Yang

Xue

Guo

et al. 2006

Biological & Pharmaceutical Bulletin

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Mammalian colon plays an important role in electrolytes and water balance, and exhibits significant segmental heterogeneity along its longitudinal axis.1) The mucosa of the colonic inner surface is a typical electrolyte-transporting epithelium, which is able to move large quantities of ion and water from the mucosal side to the blood side and vice versa.2) It has been reported that the net absorption of water, sodium and chloride, 3) as well as amiloride-sensitive shortcircuit current (I SC ) 4) was dominant in distal colon than that in proximal colon, and the same activators could induce various responses in the different segments of colon. 1,6) Nobles et al. reported that the distal segments of the rat colon were more sensitive to carbachol (CCh), a Ca 2ϩ pathway activator, as well as forskolin, a cAMP pathway activator 5) which provide the evidences for the segmental specificity with regard to the intracellular signaling pathway responsible for the activation of secretion. Using PCR technique, Greig et al. found that the expression of ENaC (epithelial Na ϩ channel) was different between the rat proximal colon and distal colon. 7)Recently, the segmental heterogeneity of endogenous prostaglandin was also reported to contribute to the differences in human colon secretory responses. 1)Ion transport in gastrointestinal tract is under the control of neurotransmitters and hormones.8) The distribution of various kinds of receptors is also different in both segments of distal and proximal colon. Norepinephrine produced segment-specific effects on ion transport via different kind of receptors. 9) However, most studies were undertaken to investigate the differences between the proximal and distal colon 3,10) or between the colon and rectum.11) During our study, we found that even within the rat distal colon, the responses difference to stimulants also existed in the different segments. But there are a limited number of studies performed to compare the distinction. In the present study, the segmental heterogeneity of epithelial responses to different stimulants and its possible mechanism were investigated in rat distal colon. MATERIALS AND METHODS SolutionsThe Ussing chamber experiments were carried out in Krebs-Henseleit solution (K-HS) contained (in mM): NaCl, 117; KCl, 4.7; MgCl 2 , 1.2; KH 2 PO 4 , 1.2; NaHCO 3 , 24.8; CaCl 2 , 2.5; glucose, 11.1. The solution was bubbled with 95% O 2 -5% CO 2 to maintain the pH of the solution at 7.4; temperature at 37°C. Tissue Preparation Animal protocols followed guidelines established by the NIH and were approved by Animal Care and Use Committee, Capital University of Medical Sciences. Adult male Sprague-Dawley rats (Laboratory Animal Services Center, Capital University of Medical Sciences) ranging in weight from 200 to 300 g had free access to standard rodent laboratory food and water until the day of the experiments. The animals were killed by cervical dislocation. The distal colon was removed and defined as the ca. 7 cmlong segment proximal to the lymph node (typically situat...

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Section: Discussionmentioning

confidence: 99%

Segmental Heterogeneity of Epithelial Ion Transport Induced by Stimulants in Rat Distal Colon

Yang

Xue

Guo

et al. 2006

Biological & Pharmaceutical Bulletin

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“…observations]. Serotonin and the serotonin 2B receptor have been implicated in key aspects of craniofacial and cardiac development [41][42][43][44]. Serotonin 2B is coupled to the G-protein Gq [45] and the ras/raf signal transduction pathway [44,46].…”

Section: Discussionmentioning

confidence: 99%

Prenatal Expression of the GLUT4 Glucose Transporter in the Mouse

et al. 2000

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The GLUT4 glucose transporter is primarily expressed in skeletal muscle, heart and adipose tissue, where its expression is postnatal, coincident with the acquisition of insulin-regulated glucose transport. In muscle, contraction also regulates GLUT4 activity in the postnatal animal. Here we demonstrate that GLUT4 is expressed in the developing mouse embryo with specific tissue and spatiotemporal patterns. From embryonic day 9 (E9; E1 = day of copulation plug) to postnatal day 70 (P70), mice were analyzed for GLUT4 mRNA and protein expression by in situ hybridization, immunohistochemistry and immunoblot. Specificity was confirmed with sense riboprobe hybridization and peptide competition, respectively. At E9, GLUT4 was detected in the cranial neural folds in the outer (mantle) layer of the neuroepithelium. At E10, expression was present throughout the developing heart and was prominent in the endocardial cushions through E12. At E10–12, GLUT4 was also prominent in craniofacial mesenchyme. GLUT4 expression in cartilage and bone was evident at E12 and was maintained throughout early postnatal life. GLUT4 was apparent throughout embryonic development in the ventricular epithelium, choroid plexus and in the developing cerebellum. At birth, cardiac expression was reduced and GLUT4 was most evident in cartilage, bone and specific brain regions. In the latter, GLUT4 expression was most evident in the cerebellum, specifically in the external granular layer through P7 and in the internal granular layer thereafter. Maximal GLUT4 protein levels in the cerebellum were measured between P14 and P21 and were reduced in the adult brain. These findings suggest that GLUT4-mediated glucose transport may play important roles during development of the brain and nonneuronal tissues in the mouse embryo.

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“…Based on earlier observations indicating that insulinlike growth factors (IGFs) are present in developing craniofacial mesenchyme together with 5-HT receptors [Lauder et al, 1994], we have recently investigated the serotonergic regulation of IGF-I and IGF-II using subtypeselective 5-HT receptor agonists and antagonists [Lambert and Lauder, 1999]. Mandibular micromass cultures grown in serum-containing medium (which contains micromolar amounts of 5-HT from serum [Argez et al, 1984]) were treated with antagonists to block binding of 5-HT to particular receptor subtypes (5-HT 1A , 5-HT 2 , 5-HT 3 and 5-HT 4 ).…”

Section: Introductionmentioning

confidence: 99%

Activation of 5-HT Receptors That Stimulate the Adenylyl Cyclase Pathway Positively Regulates IGF-I in Cultured Craniofacial Mesenchymal Cells

2001

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Results of the present study demonstrate that activation of the adenylyl cyclase/protein kinase A (PKA) pathway leads to increased levels of insulin-like growth factor I (IGF-I) in cultured embryonic mouse mandibular mesenchymal cells. Treatment of serum-free cultures with 10^–8M 8-OH-DPAT (DPAT) or with 10^–5M forskolin in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX; 10^–5M) increased levels of IGF-I (but not IGF-II), as measured by [¹²⁵I]protein A immunobinding. In a previous study, we showed that DPAT, forskolin, IBMX and the 5-HT₄ receptor agonist SC53116 all increased the synthesis of cyclic adenosine monophosphate (cAMP) in these cultures. Taken together, these results provide evidence that stimulation of the adenylyl cyclase/PKA pathway in embryonic mandibular mesenchymal cells positively regulates IGF-I. This is supported by the ability of the PKA inhibitor Rp-cAMPS to block increases in IGF-I caused by both DPAT and forskolin. Consistent with these results, DPAT and forskolin increased phosphorylation of the cAMP response element binding protein (CREB), which was also blocked by Rp-cAMPS. These results suggest that activation of 5-HT receptors positively coupled to the adenylyl cyclase/PKA pathway may promote transcription of IGF-I through a cAMP response element (CRE) in the IGF-I promoter. This may represent one mechanism whereby 5-HT positively regulates IGF-I expression in developing craniofacial mesenchymal cells.

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Serotonin Receptor Agonists That Increase Cyclic AMP Positively Regulate IGF-I in Mouse Mandibular Mesenchymal Cells

Cited by 27 publications

References 37 publications

Segmental Heterogeneity of Epithelial Ion Transport Induced by Stimulants in Rat Distal Colon

Segmental Heterogeneity of Epithelial Ion Transport Induced by Stimulants in Rat Distal Colon

Prenatal Expression of the GLUT4 Glucose Transporter in the Mouse

Activation of 5-HT Receptors That Stimulate the Adenylyl Cyclase Pathway Positively Regulates IGF-I in Cultured Craniofacial Mesenchymal Cells

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