Peptidases and smooth muscle cell angiotensin II receptor pharmacology
Angiotensin (A) II receptors on rat aortic smooth muscle (RASM) cell membranes were characterized using the radioligand [ 125I][Sar 1Ile 8]AII ([ 125I]SI-AII). Angiotensin I, AII, and AIII inhibited specific [ 125I]SI-AII binding, and their rank order of potencies, and K i values ( nM ) were: AII (3...
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| Veröffentlicht in: | Peptides (New York, N.Y. : 1980) N.Y. : 1980), 1993-03, Vol.14 (2), p.345-352 |
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| creator | Cohen, Robert B. Webb, Maria L. Dickinson, Kenneth E.J. |
| description | Angiotensin (A) II receptors on rat aortic smooth muscle (RASM) cell membranes were characterized using the radioligand [
125I][Sar
1Ile
8]AII ([
125I]SI-AII). Angiotensin I, AII, and AIII inhibited specific [
125I]SI-AII binding, and their rank order of potencies, and
K
i
values (
nM
) were:
AII (3.7) > AI (32.5) ≥ AIII RASM (54.0)
, which differed from that observed for rat adrenal cortex:
AII (0.85) > AIII (3.3) ⪢ AI (100)
. Similar results were observed for membranes in the presence of guanine nucleotides and for intact cells in the absence or presence of an internalization inhibitor. Lowering the incubation temperature from 37°C to 4°C, or inclusion of PMSF (1 n
M), and preparing membranes in the presence of EGTA (1 m
M) altered the rank order of potencies and
K
i
values (n
M) of the angiotensin peptides to:
AII (1.1) > AIII (7.0) ⪢ AI (144)
. [
125I]Angiotensin I was metabolized completely over the course of 90 min to small ( |
| doi_str_mv | 10.1016/0196-9781(93)90051-H |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_75708412</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>019697819390051H</els_id><sourcerecordid>75708412</sourcerecordid><originalsourceid>FETCH-LOGICAL-c386t-53e1e5cffdabbf679a7aee342dfebf8d7ae094e387a934fbdca9d1e507dd48f63</originalsourceid><addsrcrecordid>eNp9kE1LAzEQhoMotX78A4U9iOhhNWmym-QiSLG2IOhBzyGbTDSyu6nJVvDfm9rSo6dhZp53GB6Ezgi-IZjUt5jIupRckCtJryXGFSnne2hMBKdlRWq5j8Y75BAdpfSJMWZMihEaCSaoIJMxmr3AcvBWJ0iF7m2RuhCGj6JbJdNCYaBt8_jdhwH65PtisSgimBwJsVh-6NhpE9rw_nOCDpxuE5xu6zF6mz28Tufl0_PjYnr_VBoq6qGsKBCojHNWN42rudRcA1A2sQ4aJ2zusGRABdeSMtdYo6XNCcytZcLV9Bhdbu4uY_haQRpU59P6S91DWCXFK44FI5MMsg1oYkgpglPL6DsdfxTBaq1Prd2otRslqfrTp-Y5dr69v2o6sLvQ1lfeX2z3Ohnduqh749MOY3Ut5YRn7G6DQXbx7SGqZDz0BqzP-gZlg___j1-Y6Y2r</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>75708412</pqid></control><display><type>article</type><title>Peptidases and smooth muscle cell angiotensin II receptor pharmacology</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Cohen, Robert B. ; Webb, Maria L. ; Dickinson, Kenneth E.J.</creator><creatorcontrib>Cohen, Robert B. ; Webb, Maria L. ; Dickinson, Kenneth E.J.</creatorcontrib><description>Angiotensin (A) II receptors on rat aortic smooth muscle (RASM) cell membranes were characterized using the radioligand [
125I][Sar
1Ile
8]AII ([
125I]SI-AII). Angiotensin I, AII, and AIII inhibited specific [
125I]SI-AII binding, and their rank order of potencies, and
K
i
values (
nM
) were:
AII (3.7) > AI (32.5) ≥ AIII RASM (54.0)
, which differed from that observed for rat adrenal cortex:
AII (0.85) > AIII (3.3) ⪢ AI (100)
. Similar results were observed for membranes in the presence of guanine nucleotides and for intact cells in the absence or presence of an internalization inhibitor. Lowering the incubation temperature from 37°C to 4°C, or inclusion of PMSF (1 n
M), and preparing membranes in the presence of EGTA (1 m
M) altered the rank order of potencies and
K
i
values (n
M) of the angiotensin peptides to:
AII (1.1) > AIII (7.0) ⪢ AI (144)
. [
125I]Angiotensin I was metabolized completely over the course of 90 min to small (<tetrapeptide) fragments as measured by HPLC. There was no evidence for formation of AII or AIII from AI, which would have explained the unusually high potency of AI. [
125I]Angiotensin I metabolism could be attenuated by inhibitors of serine proteases PMSF, aprotinin, and chymostatin. The beneficial effects of PMSF and EGTA suggested that serine protease(s) and metalloproteases contribute to the observed anomalous pharmacological characteristics of AI and AIII, respectively. The RASM cell membranes contained a homogenous population of binding sites for losartan, and its
K
i
value differed in the absence (50 n
M) or presence (16 n
M) of protease inhibitors, which suggests that the receptor may also be a target for these peptidases. These data indicate that the significant angiotensinase activity of RASM cell preparations can markedly influence the potencies of angiotensin peptides and nonpeptidic antagonists.</description><identifier>ISSN: 0196-9781</identifier><identifier>EISSN: 1873-5169</identifier><identifier>DOI: 10.1016/0196-9781(93)90051-H</identifier><identifier>PMID: 8483812</identifier><identifier>CODEN: PPTDD5</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adrenal Cortex - metabolism ; Angiotensin I - metabolism ; Angiotensin II - metabolism ; Angiotensin II receptor ; Angiotensin III - metabolism ; Animals ; Biological and medical sciences ; Cell Membrane - metabolism ; Cell receptors ; Cell structures and functions ; Cells, Cultured ; Endopeptidases - metabolism ; Fundamental and applied biological sciences. Psychology ; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors ; In Vitro Techniques ; Kinetics ; Losartan ; Molecular and cellular biology ; Muscle, Smooth, Vascular - metabolism ; Protease inhibitors ; Protease Inhibitors - pharmacology ; Rats ; Receptors, Angiotensin - drug effects ; Receptors, Angiotensin - metabolism ; Saralasin - metabolism ; Smooth muscle cells</subject><ispartof>Peptides (New York, N.Y. : 1980), 1993-03, Vol.14 (2), p.345-352</ispartof><rights>1993</rights><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-53e1e5cffdabbf679a7aee342dfebf8d7ae094e387a934fbdca9d1e507dd48f63</citedby><cites>FETCH-LOGICAL-c386t-53e1e5cffdabbf679a7aee342dfebf8d7ae094e387a934fbdca9d1e507dd48f63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0196-9781(93)90051-H$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4669927$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8483812$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cohen, Robert B.</creatorcontrib><creatorcontrib>Webb, Maria L.</creatorcontrib><creatorcontrib>Dickinson, Kenneth E.J.</creatorcontrib><title>Peptidases and smooth muscle cell angiotensin II receptor pharmacology</title><title>Peptides (New York, N.Y. : 1980)</title><addtitle>Peptides</addtitle><description>Angiotensin (A) II receptors on rat aortic smooth muscle (RASM) cell membranes were characterized using the radioligand [
125I][Sar
1Ile
8]AII ([
125I]SI-AII). Angiotensin I, AII, and AIII inhibited specific [
125I]SI-AII binding, and their rank order of potencies, and
K
i
values (
nM
) were:
AII (3.7) > AI (32.5) ≥ AIII RASM (54.0)
, which differed from that observed for rat adrenal cortex:
AII (0.85) > AIII (3.3) ⪢ AI (100)
. Similar results were observed for membranes in the presence of guanine nucleotides and for intact cells in the absence or presence of an internalization inhibitor. Lowering the incubation temperature from 37°C to 4°C, or inclusion of PMSF (1 n
M), and preparing membranes in the presence of EGTA (1 m
M) altered the rank order of potencies and
K
i
values (n
M) of the angiotensin peptides to:
AII (1.1) > AIII (7.0) ⪢ AI (144)
. [
125I]Angiotensin I was metabolized completely over the course of 90 min to small (<tetrapeptide) fragments as measured by HPLC. There was no evidence for formation of AII or AIII from AI, which would have explained the unusually high potency of AI. [
125I]Angiotensin I metabolism could be attenuated by inhibitors of serine proteases PMSF, aprotinin, and chymostatin. The beneficial effects of PMSF and EGTA suggested that serine protease(s) and metalloproteases contribute to the observed anomalous pharmacological characteristics of AI and AIII, respectively. The RASM cell membranes contained a homogenous population of binding sites for losartan, and its
K
i
value differed in the absence (50 n
M) or presence (16 n
M) of protease inhibitors, which suggests that the receptor may also be a target for these peptidases. These data indicate that the significant angiotensinase activity of RASM cell preparations can markedly influence the potencies of angiotensin peptides and nonpeptidic antagonists.</description><subject>Adrenal Cortex - metabolism</subject><subject>Angiotensin I - metabolism</subject><subject>Angiotensin II - metabolism</subject><subject>Angiotensin II receptor</subject><subject>Angiotensin III - metabolism</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Membrane - metabolism</subject><subject>Cell receptors</subject><subject>Cell structures and functions</subject><subject>Cells, Cultured</subject><subject>Endopeptidases - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors</subject><subject>In Vitro Techniques</subject><subject>Kinetics</subject><subject>Losartan</subject><subject>Molecular and cellular biology</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Protease inhibitors</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Rats</subject><subject>Receptors, Angiotensin - drug effects</subject><subject>Receptors, Angiotensin - metabolism</subject><subject>Saralasin - metabolism</subject><subject>Smooth muscle cells</subject><issn>0196-9781</issn><issn>1873-5169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LAzEQhoMotX78A4U9iOhhNWmym-QiSLG2IOhBzyGbTDSyu6nJVvDfm9rSo6dhZp53GB6Ezgi-IZjUt5jIupRckCtJryXGFSnne2hMBKdlRWq5j8Y75BAdpfSJMWZMihEaCSaoIJMxmr3AcvBWJ0iF7m2RuhCGj6JbJdNCYaBt8_jdhwH65PtisSgimBwJsVh-6NhpE9rw_nOCDpxuE5xu6zF6mz28Tufl0_PjYnr_VBoq6qGsKBCojHNWN42rudRcA1A2sQ4aJ2zusGRABdeSMtdYo6XNCcytZcLV9Bhdbu4uY_haQRpU59P6S91DWCXFK44FI5MMsg1oYkgpglPL6DsdfxTBaq1Prd2otRslqfrTp-Y5dr69v2o6sLvQ1lfeX2z3Ohnduqh749MOY3Ut5YRn7G6DQXbx7SGqZDz0BqzP-gZlg___j1-Y6Y2r</recordid><startdate>19930301</startdate><enddate>19930301</enddate><creator>Cohen, Robert B.</creator><creator>Webb, Maria L.</creator><creator>Dickinson, Kenneth E.J.</creator><general>Elsevier Inc</general><general>Elsevier Science</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>19930301</creationdate><title>Peptidases and smooth muscle cell angiotensin II receptor pharmacology</title><author>Cohen, Robert B. ; Webb, Maria L. ; Dickinson, Kenneth E.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-53e1e5cffdabbf679a7aee342dfebf8d7ae094e387a934fbdca9d1e507dd48f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Adrenal Cortex - metabolism</topic><topic>Angiotensin I - metabolism</topic><topic>Angiotensin II - metabolism</topic><topic>Angiotensin II receptor</topic><topic>Angiotensin III - metabolism</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Membrane - metabolism</topic><topic>Cell receptors</topic><topic>Cell structures and functions</topic><topic>Cells, Cultured</topic><topic>Endopeptidases - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors</topic><topic>In Vitro Techniques</topic><topic>Kinetics</topic><topic>Losartan</topic><topic>Molecular and cellular biology</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Protease inhibitors</topic><topic>Protease Inhibitors - pharmacology</topic><topic>Rats</topic><topic>Receptors, Angiotensin - drug effects</topic><topic>Receptors, Angiotensin - metabolism</topic><topic>Saralasin - metabolism</topic><topic>Smooth muscle cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cohen, Robert B.</creatorcontrib><creatorcontrib>Webb, Maria L.</creatorcontrib><creatorcontrib>Dickinson, Kenneth E.J.</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>Peptides (New York, N.Y. : 1980)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cohen, Robert B.</au><au>Webb, Maria L.</au><au>Dickinson, Kenneth E.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Peptidases and smooth muscle cell angiotensin II receptor pharmacology</atitle><jtitle>Peptides (New York, N.Y. : 1980)</jtitle><addtitle>Peptides</addtitle><date>1993-03-01</date><risdate>1993</risdate><volume>14</volume><issue>2</issue><spage>345</spage><epage>352</epage><pages>345-352</pages><issn>0196-9781</issn><eissn>1873-5169</eissn><coden>PPTDD5</coden><abstract>Angiotensin (A) II receptors on rat aortic smooth muscle (RASM) cell membranes were characterized using the radioligand [
125I][Sar
1Ile
8]AII ([
125I]SI-AII). Angiotensin I, AII, and AIII inhibited specific [
125I]SI-AII binding, and their rank order of potencies, and
K
i
values (
nM
) were:
AII (3.7) > AI (32.5) ≥ AIII RASM (54.0)
, which differed from that observed for rat adrenal cortex:
AII (0.85) > AIII (3.3) ⪢ AI (100)
. Similar results were observed for membranes in the presence of guanine nucleotides and for intact cells in the absence or presence of an internalization inhibitor. Lowering the incubation temperature from 37°C to 4°C, or inclusion of PMSF (1 n
M), and preparing membranes in the presence of EGTA (1 m
M) altered the rank order of potencies and
K
i
values (n
M) of the angiotensin peptides to:
AII (1.1) > AIII (7.0) ⪢ AI (144)
. [
125I]Angiotensin I was metabolized completely over the course of 90 min to small (<tetrapeptide) fragments as measured by HPLC. There was no evidence for formation of AII or AIII from AI, which would have explained the unusually high potency of AI. [
125I]Angiotensin I metabolism could be attenuated by inhibitors of serine proteases PMSF, aprotinin, and chymostatin. The beneficial effects of PMSF and EGTA suggested that serine protease(s) and metalloproteases contribute to the observed anomalous pharmacological characteristics of AI and AIII, respectively. The RASM cell membranes contained a homogenous population of binding sites for losartan, and its
K
i
value differed in the absence (50 n
M) or presence (16 n
M) of protease inhibitors, which suggests that the receptor may also be a target for these peptidases. These data indicate that the significant angiotensinase activity of RASM cell preparations can markedly influence the potencies of angiotensin peptides and nonpeptidic antagonists.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>8483812</pmid><doi>10.1016/0196-9781(93)90051-H</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0196-9781 |
| ispartof | Peptides (New York, N.Y. : 1980), 1993-03, Vol.14 (2), p.345-352 |
| issn | 0196-9781 1873-5169 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_75708412 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adrenal Cortex - metabolism Angiotensin I - metabolism Angiotensin II - metabolism Angiotensin II receptor Angiotensin III - metabolism Animals Biological and medical sciences Cell Membrane - metabolism Cell receptors Cell structures and functions Cells, Cultured Endopeptidases - metabolism Fundamental and applied biological sciences. Psychology Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors In Vitro Techniques Kinetics Losartan Molecular and cellular biology Muscle, Smooth, Vascular - metabolism Protease inhibitors Protease Inhibitors - pharmacology Rats Receptors, Angiotensin - drug effects Receptors, Angiotensin - metabolism Saralasin - metabolism Smooth muscle cells |
| title | Peptidases and smooth muscle cell angiotensin II receptor pharmacology |
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