PACAP mediates the neural proliferative pathway of Mastomys Enterochromaffin-like cell transformation
Background and aim: Pituitary adenylate-cyclase activating peptide (PACAP) is a more potent proliferative agent than gastrin for rat enterochromaffin-like (ECL) cell proliferation in vitro. The role of this neurotransmitter during gastrin-mediated ECL cell tumor formation and gastrin-autonomous ECL...
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| Veröffentlicht in: | Regulatory peptides 2001, Vol.102 (2), p.157-164 |
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| creator | Läuffer, Jörg M Tang, Laura H Zhang, Tong Hinoue, Toshinori Rahbar, Shala Odo, Masaharu Modlin, Irvin M Kidd, Mark |
| description | Background and aim: Pituitary adenylate-cyclase activating peptide (PACAP) is a more potent proliferative agent than gastrin for rat enterochromaffin-like (ECL) cell proliferation in vitro. The role of this neurotransmitter during gastrin-mediated ECL cell tumor formation and gastrin-autonomous ECL cell neoplasia is unknown.
Methods and results: ECL cell transformation was induced in the Mastomys using 16 wk H
2 receptor blockade of acid inhibition. Examination of the epithelial fundic mucosa demonstrated that PACAP-immunoreactivity significantly increased in the tumor mucosa compared to the naı̈ve stomach, and was associated with ECL cells. Naı̈ve and tumor ECL cells were then purified (∼95%) from Mastomys and the presence of all three PACAP/VPAC receptor subtypes was demonstrated by polymerase chain-reaction amplification. Thereafter, cells were maintained in short-term (48 h) primary cultures. PACAP significantly (
p |
| doi_str_mv | 10.1016/S0167-0115(01)00314-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_72323900</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0167011501003147</els_id><sourcerecordid>72323900</sourcerecordid><originalsourceid>FETCH-LOGICAL-c486t-f9f2a04d02b6ebd06e9dbc996143c684c18a20f98a834e9f28c9464a41e4264f3</originalsourceid><addsrcrecordid>eNqFkU1vEzEQhi0EomngJ4B8AZXDgr32eu0TiqLyIRVRCThbE-9YMeyug-0U5d_jNBE9cpm5PK_n1WNCXnD2ljOu3n2ro28Y590V428YE1w2_SOy4LoXDVdaPSaLf8gFucz5J2O863vxlFxw3gtmtF4QvF2tV7d0wiFAwUzLFumM-wQj3aU4Bo8JSrhDuoOy_QMHGj39ArnE6ZDp9VwwRbdNcQLvw9yM4RdSh-NIS4I5-5immo7zM_LEw5jx-XkvyY8P19_Xn5qbrx8_r1c3jZNalcYb3wKTA2s3CjcDU2iGjTNGcSmc0tJxDS3zRoMWEiusnZFKguQoWyW9WJLXp3dr9997zMVOIR_7wIxxn23filaYKmtJuhPoUsw5obe7FCZIB8uZPfq1937tUV4d9t6v7Wvu5fnAflOdPaTOQivw6gxAdjD6qsGF_MBJ3nWmk5V7f-Kw6rgLmGx2AWdX_yGhK3aI4T9V_gIof5gz</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>72323900</pqid></control><display><type>article</type><title>PACAP mediates the neural proliferative pathway of Mastomys Enterochromaffin-like cell transformation</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Läuffer, Jörg M ; Tang, Laura H ; Zhang, Tong ; Hinoue, Toshinori ; Rahbar, Shala ; Odo, Masaharu ; Modlin, Irvin M ; Kidd, Mark</creator><creatorcontrib>Läuffer, Jörg M ; Tang, Laura H ; Zhang, Tong ; Hinoue, Toshinori ; Rahbar, Shala ; Odo, Masaharu ; Modlin, Irvin M ; Kidd, Mark</creatorcontrib><description>Background and aim: Pituitary adenylate-cyclase activating peptide (PACAP) is a more potent proliferative agent than gastrin for rat enterochromaffin-like (ECL) cell proliferation in vitro. The role of this neurotransmitter during gastrin-mediated ECL cell tumor formation and gastrin-autonomous ECL cell neoplasia is unknown.
Methods and results: ECL cell transformation was induced in the Mastomys using 16 wk H
2 receptor blockade of acid inhibition. Examination of the epithelial fundic mucosa demonstrated that PACAP-immunoreactivity significantly increased in the tumor mucosa compared to the naı̈ve stomach, and was associated with ECL cells. Naı̈ve and tumor ECL cells were then purified (∼95%) from Mastomys and the presence of all three PACAP/VPAC receptor subtypes was demonstrated by polymerase chain-reaction amplification. Thereafter, cells were maintained in short-term (48 h) primary cultures. PACAP significantly (
p<0.05) increased 24 h bromo-deoxyuridine uptake (∼4-fold) in both cell types with estimated EC
50 values of ∼4×10
−16 M and ∼2×10
−16 M, respectively. Specific receptor antagonists (PAC
1/VPAC
1) of PACAP competitively inhibited these proliferative effects in naı̈ve cells. Oligonucleotide antisense directed against PAC
1 significantly inhibited PACAP-stimulated DNA synthesis by ∼85% (
p<0.05) in tumor cells.
Conclusion: PACAP is a potent and effective modulator of ECL cell proliferation. The expression of this neuropeptide and its receptors, particularly PAC
1, suggest the existence of a neural regulatory pathway of ECL cell proliferation and transformation.</description><identifier>ISSN: 0167-0115</identifier><identifier>EISSN: 1873-1686</identifier><identifier>DOI: 10.1016/S0167-0115(01)00314-7</identifier><identifier>PMID: 11730988</identifier><identifier>CODEN: REPPDY</identifier><language>eng</language><publisher>Shannon: Elsevier B.V</publisher><subject>Animals ; Biological and medical sciences ; Carcinoid ; Cell Division - drug effects ; Cell Transformation, Neoplastic - drug effects ; Cell Transformation, Neoplastic - metabolism ; Cell Transformation, Neoplastic - pathology ; Cells, Cultured ; DNA - biosynthesis ; ECL cell ; Enterochromaffin-like Cells - metabolism ; Enterochromaffin-like Cells - pathology ; Gastric Mucosa - drug effects ; Gastric Mucosa - innervation ; Gastric Mucosa - metabolism ; Gastric Mucosa - pathology ; Gastrin ; General aspects (metabolism, cell proliferation, established cell line...) ; Humans ; Mastomys ; Medical sciences ; Microscopy, Fluorescence ; Muridae ; Neural Pathways - drug effects ; Neuropeptides - immunology ; Neuropeptides - metabolism ; Neuropeptides - pharmacology ; PACAP ; Pituitary Adenylate Cyclase-Activating Polypeptide ; Proliferation ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I ; Receptors, Pituitary Hormone - antagonists & inhibitors ; Receptors, Pituitary Hormone - genetics ; Receptors, Pituitary Hormone - metabolism ; Receptors, Vasoactive Intestinal Polypeptide, Type I ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Stomach Neoplasms - metabolism ; Stomach Neoplasms - pathology ; TGFα ; Tumor cell ; Tumor Cells, Cultured ; Tumors ; VIP</subject><ispartof>Regulatory peptides, 2001, Vol.102 (2), p.157-164</ispartof><rights>2001 Elsevier Science B.V.</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-f9f2a04d02b6ebd06e9dbc996143c684c18a20f98a834e9f28c9464a41e4264f3</citedby><cites>FETCH-LOGICAL-c486t-f9f2a04d02b6ebd06e9dbc996143c684c18a20f98a834e9f28c9464a41e4264f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0167-0115(01)00314-7$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,4009,27902,27903,27904,45974</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14155954$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11730988$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Läuffer, Jörg M</creatorcontrib><creatorcontrib>Tang, Laura H</creatorcontrib><creatorcontrib>Zhang, Tong</creatorcontrib><creatorcontrib>Hinoue, Toshinori</creatorcontrib><creatorcontrib>Rahbar, Shala</creatorcontrib><creatorcontrib>Odo, Masaharu</creatorcontrib><creatorcontrib>Modlin, Irvin M</creatorcontrib><creatorcontrib>Kidd, Mark</creatorcontrib><title>PACAP mediates the neural proliferative pathway of Mastomys Enterochromaffin-like cell transformation</title><title>Regulatory peptides</title><addtitle>Regul Pept</addtitle><description>Background and aim: Pituitary adenylate-cyclase activating peptide (PACAP) is a more potent proliferative agent than gastrin for rat enterochromaffin-like (ECL) cell proliferation in vitro. The role of this neurotransmitter during gastrin-mediated ECL cell tumor formation and gastrin-autonomous ECL cell neoplasia is unknown.
Methods and results: ECL cell transformation was induced in the Mastomys using 16 wk H
2 receptor blockade of acid inhibition. Examination of the epithelial fundic mucosa demonstrated that PACAP-immunoreactivity significantly increased in the tumor mucosa compared to the naı̈ve stomach, and was associated with ECL cells. Naı̈ve and tumor ECL cells were then purified (∼95%) from Mastomys and the presence of all three PACAP/VPAC receptor subtypes was demonstrated by polymerase chain-reaction amplification. Thereafter, cells were maintained in short-term (48 h) primary cultures. PACAP significantly (
p<0.05) increased 24 h bromo-deoxyuridine uptake (∼4-fold) in both cell types with estimated EC
50 values of ∼4×10
−16 M and ∼2×10
−16 M, respectively. Specific receptor antagonists (PAC
1/VPAC
1) of PACAP competitively inhibited these proliferative effects in naı̈ve cells. Oligonucleotide antisense directed against PAC
1 significantly inhibited PACAP-stimulated DNA synthesis by ∼85% (
p<0.05) in tumor cells.
Conclusion: PACAP is a potent and effective modulator of ECL cell proliferation. The expression of this neuropeptide and its receptors, particularly PAC
1, suggest the existence of a neural regulatory pathway of ECL cell proliferation and transformation.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Carcinoid</subject><subject>Cell Division - drug effects</subject><subject>Cell Transformation, Neoplastic - drug effects</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Cell Transformation, Neoplastic - pathology</subject><subject>Cells, Cultured</subject><subject>DNA - biosynthesis</subject><subject>ECL cell</subject><subject>Enterochromaffin-like Cells - metabolism</subject><subject>Enterochromaffin-like Cells - pathology</subject><subject>Gastric Mucosa - drug effects</subject><subject>Gastric Mucosa - innervation</subject><subject>Gastric Mucosa - metabolism</subject><subject>Gastric Mucosa - pathology</subject><subject>Gastrin</subject><subject>General aspects (metabolism, cell proliferation, established cell line...)</subject><subject>Humans</subject><subject>Mastomys</subject><subject>Medical sciences</subject><subject>Microscopy, Fluorescence</subject><subject>Muridae</subject><subject>Neural Pathways - drug effects</subject><subject>Neuropeptides - immunology</subject><subject>Neuropeptides - metabolism</subject><subject>Neuropeptides - pharmacology</subject><subject>PACAP</subject><subject>Pituitary Adenylate Cyclase-Activating Polypeptide</subject><subject>Proliferation</subject><subject>Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide</subject><subject>Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I</subject><subject>Receptors, Pituitary Hormone - antagonists & inhibitors</subject><subject>Receptors, Pituitary Hormone - genetics</subject><subject>Receptors, Pituitary Hormone - metabolism</subject><subject>Receptors, Vasoactive Intestinal Polypeptide, Type I</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Stomach Neoplasms - metabolism</subject><subject>Stomach Neoplasms - pathology</subject><subject>TGFα</subject><subject>Tumor cell</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><subject>VIP</subject><issn>0167-0115</issn><issn>1873-1686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vEzEQhi0EomngJ4B8AZXDgr32eu0TiqLyIRVRCThbE-9YMeyug-0U5d_jNBE9cpm5PK_n1WNCXnD2ljOu3n2ro28Y590V428YE1w2_SOy4LoXDVdaPSaLf8gFucz5J2O863vxlFxw3gtmtF4QvF2tV7d0wiFAwUzLFumM-wQj3aU4Bo8JSrhDuoOy_QMHGj39ArnE6ZDp9VwwRbdNcQLvw9yM4RdSh-NIS4I5-5immo7zM_LEw5jx-XkvyY8P19_Xn5qbrx8_r1c3jZNalcYb3wKTA2s3CjcDU2iGjTNGcSmc0tJxDS3zRoMWEiusnZFKguQoWyW9WJLXp3dr9997zMVOIR_7wIxxn23filaYKmtJuhPoUsw5obe7FCZIB8uZPfq1937tUV4d9t6v7Wvu5fnAflOdPaTOQivw6gxAdjD6qsGF_MBJ3nWmk5V7f-Kw6rgLmGx2AWdX_yGhK3aI4T9V_gIof5gz</recordid><startdate>2001</startdate><enddate>2001</enddate><creator>Läuffer, Jörg M</creator><creator>Tang, Laura H</creator><creator>Zhang, Tong</creator><creator>Hinoue, Toshinori</creator><creator>Rahbar, Shala</creator><creator>Odo, Masaharu</creator><creator>Modlin, Irvin M</creator><creator>Kidd, Mark</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>2001</creationdate><title>PACAP mediates the neural proliferative pathway of Mastomys Enterochromaffin-like cell transformation</title><author>Läuffer, Jörg M ; Tang, Laura H ; Zhang, Tong ; Hinoue, Toshinori ; Rahbar, Shala ; Odo, Masaharu ; Modlin, Irvin M ; Kidd, Mark</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-f9f2a04d02b6ebd06e9dbc996143c684c18a20f98a834e9f28c9464a41e4264f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Carcinoid</topic><topic>Cell Division - drug effects</topic><topic>Cell Transformation, Neoplastic - drug effects</topic><topic>Cell Transformation, Neoplastic - metabolism</topic><topic>Cell Transformation, Neoplastic - pathology</topic><topic>Cells, Cultured</topic><topic>DNA - biosynthesis</topic><topic>ECL cell</topic><topic>Enterochromaffin-like Cells - metabolism</topic><topic>Enterochromaffin-like Cells - pathology</topic><topic>Gastric Mucosa - drug effects</topic><topic>Gastric Mucosa - innervation</topic><topic>Gastric Mucosa - metabolism</topic><topic>Gastric Mucosa - pathology</topic><topic>Gastrin</topic><topic>General aspects (metabolism, cell proliferation, established cell line...)</topic><topic>Humans</topic><topic>Mastomys</topic><topic>Medical sciences</topic><topic>Microscopy, Fluorescence</topic><topic>Muridae</topic><topic>Neural Pathways - drug effects</topic><topic>Neuropeptides - immunology</topic><topic>Neuropeptides - metabolism</topic><topic>Neuropeptides - pharmacology</topic><topic>PACAP</topic><topic>Pituitary Adenylate Cyclase-Activating Polypeptide</topic><topic>Proliferation</topic><topic>Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide</topic><topic>Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I</topic><topic>Receptors, Pituitary Hormone - antagonists & inhibitors</topic><topic>Receptors, Pituitary Hormone - genetics</topic><topic>Receptors, Pituitary Hormone - metabolism</topic><topic>Receptors, Vasoactive Intestinal Polypeptide, Type I</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Stomach Neoplasms - metabolism</topic><topic>Stomach Neoplasms - pathology</topic><topic>TGFα</topic><topic>Tumor cell</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><topic>VIP</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Läuffer, Jörg M</creatorcontrib><creatorcontrib>Tang, Laura H</creatorcontrib><creatorcontrib>Zhang, Tong</creatorcontrib><creatorcontrib>Hinoue, Toshinori</creatorcontrib><creatorcontrib>Rahbar, Shala</creatorcontrib><creatorcontrib>Odo, Masaharu</creatorcontrib><creatorcontrib>Modlin, Irvin M</creatorcontrib><creatorcontrib>Kidd, Mark</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Regulatory peptides</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Läuffer, Jörg M</au><au>Tang, Laura H</au><au>Zhang, Tong</au><au>Hinoue, Toshinori</au><au>Rahbar, Shala</au><au>Odo, Masaharu</au><au>Modlin, Irvin M</au><au>Kidd, Mark</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PACAP mediates the neural proliferative pathway of Mastomys Enterochromaffin-like cell transformation</atitle><jtitle>Regulatory peptides</jtitle><addtitle>Regul Pept</addtitle><date>2001</date><risdate>2001</risdate><volume>102</volume><issue>2</issue><spage>157</spage><epage>164</epage><pages>157-164</pages><issn>0167-0115</issn><eissn>1873-1686</eissn><coden>REPPDY</coden><abstract>Background and aim: Pituitary adenylate-cyclase activating peptide (PACAP) is a more potent proliferative agent than gastrin for rat enterochromaffin-like (ECL) cell proliferation in vitro. The role of this neurotransmitter during gastrin-mediated ECL cell tumor formation and gastrin-autonomous ECL cell neoplasia is unknown.
Methods and results: ECL cell transformation was induced in the Mastomys using 16 wk H
2 receptor blockade of acid inhibition. Examination of the epithelial fundic mucosa demonstrated that PACAP-immunoreactivity significantly increased in the tumor mucosa compared to the naı̈ve stomach, and was associated with ECL cells. Naı̈ve and tumor ECL cells were then purified (∼95%) from Mastomys and the presence of all three PACAP/VPAC receptor subtypes was demonstrated by polymerase chain-reaction amplification. Thereafter, cells were maintained in short-term (48 h) primary cultures. PACAP significantly (
p<0.05) increased 24 h bromo-deoxyuridine uptake (∼4-fold) in both cell types with estimated EC
50 values of ∼4×10
−16 M and ∼2×10
−16 M, respectively. Specific receptor antagonists (PAC
1/VPAC
1) of PACAP competitively inhibited these proliferative effects in naı̈ve cells. Oligonucleotide antisense directed against PAC
1 significantly inhibited PACAP-stimulated DNA synthesis by ∼85% (
p<0.05) in tumor cells.
Conclusion: PACAP is a potent and effective modulator of ECL cell proliferation. The expression of this neuropeptide and its receptors, particularly PAC
1, suggest the existence of a neural regulatory pathway of ECL cell proliferation and transformation.</abstract><cop>Shannon</cop><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>11730988</pmid><doi>10.1016/S0167-0115(01)00314-7</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-0115 |
| ispartof | Regulatory peptides, 2001, Vol.102 (2), p.157-164 |
| issn | 0167-0115 1873-1686 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_72323900 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Biological and medical sciences Carcinoid Cell Division - drug effects Cell Transformation, Neoplastic - drug effects Cell Transformation, Neoplastic - metabolism Cell Transformation, Neoplastic - pathology Cells, Cultured DNA - biosynthesis ECL cell Enterochromaffin-like Cells - metabolism Enterochromaffin-like Cells - pathology Gastric Mucosa - drug effects Gastric Mucosa - innervation Gastric Mucosa - metabolism Gastric Mucosa - pathology Gastrin General aspects (metabolism, cell proliferation, established cell line...) Humans Mastomys Medical sciences Microscopy, Fluorescence Muridae Neural Pathways - drug effects Neuropeptides - immunology Neuropeptides - metabolism Neuropeptides - pharmacology PACAP Pituitary Adenylate Cyclase-Activating Polypeptide Proliferation Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I Receptors, Pituitary Hormone - antagonists & inhibitors Receptors, Pituitary Hormone - genetics Receptors, Pituitary Hormone - metabolism Receptors, Vasoactive Intestinal Polypeptide, Type I Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism Stomach Neoplasms - metabolism Stomach Neoplasms - pathology TGFα Tumor cell Tumor Cells, Cultured Tumors VIP |
| title | PACAP mediates the neural proliferative pathway of Mastomys Enterochromaffin-like cell transformation |
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