Desensitization of CGRP and Adrenomedullin Receptors in SK-N-MC Cells: Implications for the RAMP Hypothesis
Recent evidence (1) suggests that the related peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) bind to the same heptahelical transmembrane receptor, with receptor specificity being determined by a receptor associated modifying protein (RAMP). If correct, this hypothesis would...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 1999-01, Vol.140 (1), p.533-533 |
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| creator | Drake, W. M Ajayi, A Lowe, S. R Mirtella, A Bartlett, T. J Clark, A. J. L |
| description | Recent evidence (1) suggests that the related peptides calcitonin
gene-related peptide (CGRP) and adrenomedullin (AM) bind to the same
heptahelical transmembrane receptor, with receptor specificity being
determined by a receptor associated modifying protein (RAMP). If
correct, this hypothesis would predict that each peptide should
desensitize the cellular response to subsequent stimulation by itself
or the other peptide. We have therefore studied the patterns of
desensitization of these receptors in SK-N-MC cells. SK-N-MC cells were
stimulated for 20 minutes in either serum free medium alone (control)
or SFM containing AM 10−8M or CGRP 10−7M.
Cells were then incubated for a further 20 minutes in SFM containing a
second agonist and 1 mM isobutyryl methylxanthine (IBMX), before
harvesting and assay for cAMP. Pre-exposure of cells to CGRP or AM
decreased cAMP generation in response to subsequent stimulation with
CGRP by 58% (±14) and 42% (±14) (SD) respectively. Pre-incubation
of cells with 100 nM H-89 abolished this effect, indicating that
desensitization was mediated through PKA. In contrast, there was no
attenuation of the cAMP response to stimulation with AM by pre-exposure
to AM or CGRP. These results suggest that CGRP and AM receptors exhibit
different patterns of desensitization in SK-N-MC cells: a finding with
significant implications for the RAMP hypothesis. |
| doi_str_mv | 10.1210/endo.140.1.6606 |
| format | Article |
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gene-related peptide (CGRP) and adrenomedullin (AM) bind to the same
heptahelical transmembrane receptor, with receptor specificity being
determined by a receptor associated modifying protein (RAMP). If
correct, this hypothesis would predict that each peptide should
desensitize the cellular response to subsequent stimulation by itself
or the other peptide. We have therefore studied the patterns of
desensitization of these receptors in SK-N-MC cells. SK-N-MC cells were
stimulated for 20 minutes in either serum free medium alone (control)
or SFM containing AM 10−8M or CGRP 10−7M.
Cells were then incubated for a further 20 minutes in SFM containing a
second agonist and 1 mM isobutyryl methylxanthine (IBMX), before
harvesting and assay for cAMP. Pre-exposure of cells to CGRP or AM
decreased cAMP generation in response to subsequent stimulation with
CGRP by 58% (±14) and 42% (±14) (SD) respectively. Pre-incubation
of cells with 100 nM H-89 abolished this effect, indicating that
desensitization was mediated through PKA. In contrast, there was no
attenuation of the cAMP response to stimulation with AM by pre-exposure
to AM or CGRP. These results suggest that CGRP and AM receptors exhibit
different patterns of desensitization in SK-N-MC cells: a finding with
significant implications for the RAMP hypothesis.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/endo.140.1.6606</identifier><language>eng</language><publisher>Washington: Endocrine Society</publisher><subject>Adrenomedullin ; Calcitonin ; Calcitonin gene-related peptide ; Cell surface receptors ; Cyclic AMP ; Desensitization ; Hypotheses ; Peptides ; Protein kinase A ; Receptors ; Stimulation</subject><ispartof>Endocrinology (Philadelphia), 1999-01, Vol.140 (1), p.533-533</ispartof><rights>Copyright © 1999 by The Endocrine Society 1999</rights><rights>Copyright © 1999 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2376-d146adc36c200adcae9aabef850c8004a9c020316d1cce2554dd07693053547b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids></links><search><creatorcontrib>Drake, W. M</creatorcontrib><creatorcontrib>Ajayi, A</creatorcontrib><creatorcontrib>Lowe, S. R</creatorcontrib><creatorcontrib>Mirtella, A</creatorcontrib><creatorcontrib>Bartlett, T. J</creatorcontrib><creatorcontrib>Clark, A. J. L</creatorcontrib><title>Desensitization of CGRP and Adrenomedullin Receptors in SK-N-MC Cells: Implications for the RAMP Hypothesis</title><title>Endocrinology (Philadelphia)</title><description>Recent evidence (1) suggests that the related peptides calcitonin
gene-related peptide (CGRP) and adrenomedullin (AM) bind to the same
heptahelical transmembrane receptor, with receptor specificity being
determined by a receptor associated modifying protein (RAMP). If
correct, this hypothesis would predict that each peptide should
desensitize the cellular response to subsequent stimulation by itself
or the other peptide. We have therefore studied the patterns of
desensitization of these receptors in SK-N-MC cells. SK-N-MC cells were
stimulated for 20 minutes in either serum free medium alone (control)
or SFM containing AM 10−8M or CGRP 10−7M.
Cells were then incubated for a further 20 minutes in SFM containing a
second agonist and 1 mM isobutyryl methylxanthine (IBMX), before
harvesting and assay for cAMP. Pre-exposure of cells to CGRP or AM
decreased cAMP generation in response to subsequent stimulation with
CGRP by 58% (±14) and 42% (±14) (SD) respectively. Pre-incubation
of cells with 100 nM H-89 abolished this effect, indicating that
desensitization was mediated through PKA. In contrast, there was no
attenuation of the cAMP response to stimulation with AM by pre-exposure
to AM or CGRP. These results suggest that CGRP and AM receptors exhibit
different patterns of desensitization in SK-N-MC cells: a finding with
significant implications for the RAMP hypothesis.</description><subject>Adrenomedullin</subject><subject>Calcitonin</subject><subject>Calcitonin gene-related peptide</subject><subject>Cell surface receptors</subject><subject>Cyclic AMP</subject><subject>Desensitization</subject><subject>Hypotheses</subject><subject>Peptides</subject><subject>Protein kinase A</subject><subject>Receptors</subject><subject>Stimulation</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><recordid>eNqNkM1PwzAMxSMEEuPjzDUSN6QOp0nTldtUYCAGTAPOUZa4oqNrStId4K8nY0ickDjZP_k923qEnDAYspTBObbWDZmINJQS5A4ZsEJkSc5y2CUDAMaTPE3zfXIQwjKiEIIPyNslBmxD3defuq9dS11Fy8l8RnVr6dh6bN0K7bpp6pbO0WDXOx9ohKe75CG5L2mJTRMu6O2qa2rzvSLQynnavyKdj-9n9OajcxFCHY7IXqWbgMc_9ZC8XF89lzfJ9HFyW46niUl5LhPLhNTWcGlSgNhoLLReYDXKwIwAhC4MpMCZtMwYTLNMWAu5LDhkPBP5gh-S0-3ezrv3NYZeLd3at_Gk4oyDKLK0yKLqfKsy3oXgsVKdr1fafygGapOo2iSqYqKKqU2i0XG2dbh19w-x3Io3A-PrFjuPIfy-8pfxC5yviKo</recordid><startdate>199901</startdate><enddate>199901</enddate><creator>Drake, W. M</creator><creator>Ajayi, A</creator><creator>Lowe, S. R</creator><creator>Mirtella, A</creator><creator>Bartlett, T. J</creator><creator>Clark, A. J. L</creator><general>Endocrine Society</general><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope></search><sort><creationdate>199901</creationdate><title>Desensitization of CGRP and Adrenomedullin Receptors in SK-N-MC Cells: Implications for the RAMP Hypothesis</title><author>Drake, W. M ; Ajayi, A ; Lowe, S. R ; Mirtella, A ; Bartlett, T. J ; Clark, A. J. L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2376-d146adc36c200adcae9aabef850c8004a9c020316d1cce2554dd07693053547b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adrenomedullin</topic><topic>Calcitonin</topic><topic>Calcitonin gene-related peptide</topic><topic>Cell surface receptors</topic><topic>Cyclic AMP</topic><topic>Desensitization</topic><topic>Hypotheses</topic><topic>Peptides</topic><topic>Protein kinase A</topic><topic>Receptors</topic><topic>Stimulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Drake, W. M</creatorcontrib><creatorcontrib>Ajayi, A</creatorcontrib><creatorcontrib>Lowe, S. R</creatorcontrib><creatorcontrib>Mirtella, A</creatorcontrib><creatorcontrib>Bartlett, T. J</creatorcontrib><creatorcontrib>Clark, A. J. L</creatorcontrib><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Drake, W. M</au><au>Ajayi, A</au><au>Lowe, S. R</au><au>Mirtella, A</au><au>Bartlett, T. J</au><au>Clark, A. J. L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Desensitization of CGRP and Adrenomedullin Receptors in SK-N-MC Cells: Implications for the RAMP Hypothesis</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><date>1999-01</date><risdate>1999</risdate><volume>140</volume><issue>1</issue><spage>533</spage><epage>533</epage><pages>533-533</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><abstract>Recent evidence (1) suggests that the related peptides calcitonin
gene-related peptide (CGRP) and adrenomedullin (AM) bind to the same
heptahelical transmembrane receptor, with receptor specificity being
determined by a receptor associated modifying protein (RAMP). If
correct, this hypothesis would predict that each peptide should
desensitize the cellular response to subsequent stimulation by itself
or the other peptide. We have therefore studied the patterns of
desensitization of these receptors in SK-N-MC cells. SK-N-MC cells were
stimulated for 20 minutes in either serum free medium alone (control)
or SFM containing AM 10−8M or CGRP 10−7M.
Cells were then incubated for a further 20 minutes in SFM containing a
second agonist and 1 mM isobutyryl methylxanthine (IBMX), before
harvesting and assay for cAMP. Pre-exposure of cells to CGRP or AM
decreased cAMP generation in response to subsequent stimulation with
CGRP by 58% (±14) and 42% (±14) (SD) respectively. Pre-incubation
of cells with 100 nM H-89 abolished this effect, indicating that
desensitization was mediated through PKA. In contrast, there was no
attenuation of the cAMP response to stimulation with AM by pre-exposure
to AM or CGRP. These results suggest that CGRP and AM receptors exhibit
different patterns of desensitization in SK-N-MC cells: a finding with
significant implications for the RAMP hypothesis.</abstract><cop>Washington</cop><pub>Endocrine Society</pub><doi>10.1210/endo.140.1.6606</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Endocrinology (Philadelphia), 1999-01, Vol.140 (1), p.533-533 |
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| language | eng |
| recordid | cdi_proquest_journals_3130495295 |
| source | Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals |
| subjects | Adrenomedullin Calcitonin Calcitonin gene-related peptide Cell surface receptors Cyclic AMP Desensitization Hypotheses Peptides Protein kinase A Receptors Stimulation |
| title | Desensitization of CGRP and Adrenomedullin Receptors in SK-N-MC Cells: Implications for the RAMP Hypothesis |
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