Purinoceptor subtypes mediating contraction and relaxation of marmoset urinary bladder smooth muscle
The effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP), α,β‐methylene‐ATP (α,β‐MeATP) and 2‐methylthio‐ATP (2‐MeSATP) on longitudinally orientated smooth muscle strips from marmoset urinary bladder were investigated by use of standard organ bath techniques. After being mounted in s...
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description | The effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP), α,β‐methylene‐ATP (α,β‐MeATP) and 2‐methylthio‐ATP (2‐MeSATP) on longitudinally orientated smooth muscle strips from marmoset urinary bladder were investigated by use of standard organ bath techniques.
After being mounted in superfusion organ baths, 66.7% (n=249) of marmoset detrusor smooth muscle strips developed spontaneous tone, 48.2% of all strips examined developed tone equivalent to greater than 0.1 g mg−1 of tissue and were subsequently utilized in the present investigation.
On exposure to ATP, muscle strips exhibited a biphasic response, a rapid and transient contraction followed by a more prolonged relaxation. Both responses were found to be concentration‐dependent. ADP and 2‐MeSATP elicited a similar response (contraction followed by relaxation), whereas application of α,β‐MeATP only produced a contraction. The potency order for each effect was α,β‐MeATP>>2‐MeSATPATP>ADP (contractile response) and ATP=2‐MeSATPADP>>α,β‐MeATP (relaxational response).
Desensitization with α,β‐MeATP (10 μM) abolished the contractile phase of the response to ATP, but had no effect on the level of relaxation evoked by this agonist. On the other hand, the G‐protein inactivator, GDPβS (100 μM) abolished only the relaxation response to ATP. Suramin (general P2 antagonist, 100 μM) shifted both the contractile and relaxation ATP concentration‐response curves to the right, whereas cibacron blue (P2Y antagonist, 10 μM) only antagonized the relaxation response to ATP. In contrast, the adenosine receptor antagonist, 8‐phenyltheophylline (10 μM), had no effect on the relaxation response curve to ATP.
Incubation with tetrodotoxin (TTX, 3 μM) or depolarization of the muscle strip with 40 mM K+ Krebs failed to abolish the relaxation to ATP. In addition, neither Nω‐nitro‐L‐arginine (L‐NOARG, 10 μM) nor methylene blue (10 μM) had any effect on the relaxation response curve. However, tos‐phe‐chloromethylketone (TPCK, 3 μM), an inhibitor of cyclicAMP‐dependent protein kinase A (PKA), significantly (P |
doi_str_mv | 10.1038/sj.bjp.0701774 |
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After being mounted in superfusion organ baths, 66.7% (n=249) of marmoset detrusor smooth muscle strips developed spontaneous tone, 48.2% of all strips examined developed tone equivalent to greater than 0.1 g mg−1 of tissue and were subsequently utilized in the present investigation.
On exposure to ATP, muscle strips exhibited a biphasic response, a rapid and transient contraction followed by a more prolonged relaxation. Both responses were found to be concentration‐dependent. ADP and 2‐MeSATP elicited a similar response (contraction followed by relaxation), whereas application of α,β‐MeATP only produced a contraction. The potency order for each effect was α,β‐MeATP>>2‐MeSATPATP>ADP (contractile response) and ATP=2‐MeSATPADP>>α,β‐MeATP (relaxational response).
Desensitization with α,β‐MeATP (10 μM) abolished the contractile phase of the response to ATP, but had no effect on the level of relaxation evoked by this agonist. On the other hand, the G‐protein inactivator, GDPβS (100 μM) abolished only the relaxation response to ATP. Suramin (general P2 antagonist, 100 μM) shifted both the contractile and relaxation ATP concentration‐response curves to the right, whereas cibacron blue (P2Y antagonist, 10 μM) only antagonized the relaxation response to ATP. In contrast, the adenosine receptor antagonist, 8‐phenyltheophylline (10 μM), had no effect on the relaxation response curve to ATP.
Incubation with tetrodotoxin (TTX, 3 μM) or depolarization of the muscle strip with 40 mM K+ Krebs failed to abolish the relaxation to ATP. In addition, neither Nω‐nitro‐L‐arginine (L‐NOARG, 10 μM) nor methylene blue (10 μM) had any effect on the relaxation response curve. However, tos‐phe‐chloromethylketone (TPCK, 3 μM), an inhibitor of cyclicAMP‐dependent protein kinase A (PKA), significantly (P<0.01) shifted the curve for the ATP‐induced relaxation to the right.
It is proposed that marmoset detrusor smooth muscle contains two receptors for ATP, a classical P2X‐type receptor mediating smooth muscle contraction, and a P2Y (G‐protein linked) receptor mediating smooth muscle relaxation. The results also indicate that the ATP‐evoked relaxation may occur through the activation of cyclicAMP‐dependent PKA.
British Journal of Pharmacology (1998) 123, 1579–1586; doi:10.1038/sj.bjp.0701774</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0701774</identifier><identifier>PMID: 9605564</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adenosine Diphosphate - pharmacology ; Adenosine Triphosphate - analogs & derivatives ; Adenosine Triphosphate - pharmacology ; Adenosinic and purinergic receptors ; Animals ; ATP ; Biological and medical sciences ; Callithrix ; Cell receptors ; Cell structures and functions ; cibacron blue 3GA ; cyclicAMP ; Female ; Fundamental and applied biological sciences. Psychology ; In Vitro Techniques ; Male ; marmoset urinary bladder ; Molecular and cellular biology ; Muscle Contraction - drug effects ; Muscle Contraction - physiology ; Muscle Relaxation - drug effects ; Muscle Relaxation - physiology ; Muscle, Smooth - drug effects ; Muscle, Smooth - innervation ; Muscle, Smooth - physiology ; P2 receptors ; Receptors, Purinergic - drug effects ; Receptors, Purinergic P1 - drug effects ; Receptors, Purinergic P2 - drug effects ; smooth muscle contraction and relaxation ; suramin ; Urinary Bladder - drug effects ; Urinary Bladder - innervation ; Urinary Bladder - physiology</subject><ispartof>British journal of pharmacology, 1998-04, Vol.123 (8), p.1579-1586</ispartof><rights>1998 British Pharmacological Society</rights><rights>1998 INIST-CNRS</rights><rights>Copyright 1998, Nature Publishing Group 1998 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5248-3ded52aee4e8f3837182a398c6ed354e7cd1c3d8a8ba4ea6a10a3e8e86526ec03</citedby><cites>FETCH-LOGICAL-c5248-3ded52aee4e8f3837182a398c6ed354e7cd1c3d8a8ba4ea6a10a3e8e86526ec03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1565329/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1565329/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2226728$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9605564$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McMurray, Gordon</creatorcontrib><creatorcontrib>Dass, Narinder</creatorcontrib><creatorcontrib>Brading, Alison F.</creatorcontrib><title>Purinoceptor subtypes mediating contraction and relaxation of marmoset urinary bladder smooth muscle</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>The effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP), α,β‐methylene‐ATP (α,β‐MeATP) and 2‐methylthio‐ATP (2‐MeSATP) on longitudinally orientated smooth muscle strips from marmoset urinary bladder were investigated by use of standard organ bath techniques.
After being mounted in superfusion organ baths, 66.7% (n=249) of marmoset detrusor smooth muscle strips developed spontaneous tone, 48.2% of all strips examined developed tone equivalent to greater than 0.1 g mg−1 of tissue and were subsequently utilized in the present investigation.
On exposure to ATP, muscle strips exhibited a biphasic response, a rapid and transient contraction followed by a more prolonged relaxation. Both responses were found to be concentration‐dependent. ADP and 2‐MeSATP elicited a similar response (contraction followed by relaxation), whereas application of α,β‐MeATP only produced a contraction. The potency order for each effect was α,β‐MeATP>>2‐MeSATPATP>ADP (contractile response) and ATP=2‐MeSATPADP>>α,β‐MeATP (relaxational response).
Desensitization with α,β‐MeATP (10 μM) abolished the contractile phase of the response to ATP, but had no effect on the level of relaxation evoked by this agonist. On the other hand, the G‐protein inactivator, GDPβS (100 μM) abolished only the relaxation response to ATP. Suramin (general P2 antagonist, 100 μM) shifted both the contractile and relaxation ATP concentration‐response curves to the right, whereas cibacron blue (P2Y antagonist, 10 μM) only antagonized the relaxation response to ATP. In contrast, the adenosine receptor antagonist, 8‐phenyltheophylline (10 μM), had no effect on the relaxation response curve to ATP.
Incubation with tetrodotoxin (TTX, 3 μM) or depolarization of the muscle strip with 40 mM K+ Krebs failed to abolish the relaxation to ATP. In addition, neither Nω‐nitro‐L‐arginine (L‐NOARG, 10 μM) nor methylene blue (10 μM) had any effect on the relaxation response curve. However, tos‐phe‐chloromethylketone (TPCK, 3 μM), an inhibitor of cyclicAMP‐dependent protein kinase A (PKA), significantly (P<0.01) shifted the curve for the ATP‐induced relaxation to the right.
It is proposed that marmoset detrusor smooth muscle contains two receptors for ATP, a classical P2X‐type receptor mediating smooth muscle contraction, and a P2Y (G‐protein linked) receptor mediating smooth muscle relaxation. The results also indicate that the ATP‐evoked relaxation may occur through the activation of cyclicAMP‐dependent PKA.
British Journal of Pharmacology (1998) 123, 1579–1586; doi:10.1038/sj.bjp.0701774</description><subject>Adenosine Diphosphate - pharmacology</subject><subject>Adenosine Triphosphate - analogs & derivatives</subject><subject>Adenosine Triphosphate - pharmacology</subject><subject>Adenosinic and purinergic receptors</subject><subject>Animals</subject><subject>ATP</subject><subject>Biological and medical sciences</subject><subject>Callithrix</subject><subject>Cell receptors</subject><subject>Cell structures and functions</subject><subject>cibacron blue 3GA</subject><subject>cyclicAMP</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>marmoset urinary bladder</subject><subject>Molecular and cellular biology</subject><subject>Muscle Contraction - drug effects</subject><subject>Muscle Contraction - physiology</subject><subject>Muscle Relaxation - drug effects</subject><subject>Muscle Relaxation - physiology</subject><subject>Muscle, Smooth - drug effects</subject><subject>Muscle, Smooth - innervation</subject><subject>Muscle, Smooth - physiology</subject><subject>P2 receptors</subject><subject>Receptors, Purinergic - drug effects</subject><subject>Receptors, Purinergic P1 - drug effects</subject><subject>Receptors, Purinergic P2 - drug effects</subject><subject>smooth muscle contraction and relaxation</subject><subject>suramin</subject><subject>Urinary Bladder - drug effects</subject><subject>Urinary Bladder - innervation</subject><subject>Urinary Bladder - physiology</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v1DAQxS0EKkvhyg0pB8Qtiz_ij1yQoAKKVIke4GxN7EnrVRIHOynsf4-XXa3gxGk0ej-_edYj5CWjW0aFeZt32243b6mmTOvmEdmwRqtaCsMekw2lVNeMGfOUPMt5R2kRtbwgF62iUqpmQ_ztmsIUHc5LTFVeu2U_Y65G9AGWMN1VLk5LAreEOFUw-SrhAL_gzxr7aoQ0xoxLdXCBtK-6AbzH4jTGuNxX45rdgM_Jkx6GjC9O85J8__Tx29V1ffP185er9ze1k7wxtfDoJQfEBk0vjNDMcBCtcQq9kA1q55kT3oDpoEFQwCgINGiU5AodFZfk3dF3XrvyA4eH6IOdUyg59zZCsP8qU7i3d_HBMqmk4G0xeHMySPHHinmxY8gOhwEmjGu2ujVtozkr4PYIuhRzTtifjzBqD73YvLOlF3vqpTx49Xe0M34qouivTzpkB0OfYHIhnzHOudLcFEwcsZ9hwP1_jtoPt9eKKiN-Aza5q1g</recordid><startdate>199804</startdate><enddate>199804</enddate><creator>McMurray, Gordon</creator><creator>Dass, Narinder</creator><creator>Brading, Alison F.</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</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><scope>5PM</scope></search><sort><creationdate>199804</creationdate><title>Purinoceptor subtypes mediating contraction and relaxation of marmoset urinary bladder smooth muscle</title><author>McMurray, Gordon ; Dass, Narinder ; Brading, Alison F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5248-3ded52aee4e8f3837182a398c6ed354e7cd1c3d8a8ba4ea6a10a3e8e86526ec03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adenosine Diphosphate - pharmacology</topic><topic>Adenosine Triphosphate - analogs & derivatives</topic><topic>Adenosine Triphosphate - pharmacology</topic><topic>Adenosinic and purinergic receptors</topic><topic>Animals</topic><topic>ATP</topic><topic>Biological and medical sciences</topic><topic>Callithrix</topic><topic>Cell receptors</topic><topic>Cell structures and functions</topic><topic>cibacron blue 3GA</topic><topic>cyclicAMP</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>marmoset urinary bladder</topic><topic>Molecular and cellular biology</topic><topic>Muscle Contraction - drug effects</topic><topic>Muscle Contraction - physiology</topic><topic>Muscle Relaxation - drug effects</topic><topic>Muscle Relaxation - physiology</topic><topic>Muscle, Smooth - drug effects</topic><topic>Muscle, Smooth - innervation</topic><topic>Muscle, Smooth - physiology</topic><topic>P2 receptors</topic><topic>Receptors, Purinergic - drug effects</topic><topic>Receptors, Purinergic P1 - drug effects</topic><topic>Receptors, Purinergic P2 - drug effects</topic><topic>smooth muscle contraction and relaxation</topic><topic>suramin</topic><topic>Urinary Bladder - drug effects</topic><topic>Urinary Bladder - innervation</topic><topic>Urinary Bladder - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McMurray, Gordon</creatorcontrib><creatorcontrib>Dass, Narinder</creatorcontrib><creatorcontrib>Brading, Alison F.</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McMurray, Gordon</au><au>Dass, Narinder</au><au>Brading, Alison F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Purinoceptor subtypes mediating contraction and relaxation of marmoset urinary bladder smooth muscle</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>1998-04</date><risdate>1998</risdate><volume>123</volume><issue>8</issue><spage>1579</spage><epage>1586</epage><pages>1579-1586</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>The effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP), α,β‐methylene‐ATP (α,β‐MeATP) and 2‐methylthio‐ATP (2‐MeSATP) on longitudinally orientated smooth muscle strips from marmoset urinary bladder were investigated by use of standard organ bath techniques.
After being mounted in superfusion organ baths, 66.7% (n=249) of marmoset detrusor smooth muscle strips developed spontaneous tone, 48.2% of all strips examined developed tone equivalent to greater than 0.1 g mg−1 of tissue and were subsequently utilized in the present investigation.
On exposure to ATP, muscle strips exhibited a biphasic response, a rapid and transient contraction followed by a more prolonged relaxation. Both responses were found to be concentration‐dependent. ADP and 2‐MeSATP elicited a similar response (contraction followed by relaxation), whereas application of α,β‐MeATP only produced a contraction. The potency order for each effect was α,β‐MeATP>>2‐MeSATPATP>ADP (contractile response) and ATP=2‐MeSATPADP>>α,β‐MeATP (relaxational response).
Desensitization with α,β‐MeATP (10 μM) abolished the contractile phase of the response to ATP, but had no effect on the level of relaxation evoked by this agonist. On the other hand, the G‐protein inactivator, GDPβS (100 μM) abolished only the relaxation response to ATP. Suramin (general P2 antagonist, 100 μM) shifted both the contractile and relaxation ATP concentration‐response curves to the right, whereas cibacron blue (P2Y antagonist, 10 μM) only antagonized the relaxation response to ATP. In contrast, the adenosine receptor antagonist, 8‐phenyltheophylline (10 μM), had no effect on the relaxation response curve to ATP.
Incubation with tetrodotoxin (TTX, 3 μM) or depolarization of the muscle strip with 40 mM K+ Krebs failed to abolish the relaxation to ATP. In addition, neither Nω‐nitro‐L‐arginine (L‐NOARG, 10 μM) nor methylene blue (10 μM) had any effect on the relaxation response curve. However, tos‐phe‐chloromethylketone (TPCK, 3 μM), an inhibitor of cyclicAMP‐dependent protein kinase A (PKA), significantly (P<0.01) shifted the curve for the ATP‐induced relaxation to the right.
It is proposed that marmoset detrusor smooth muscle contains two receptors for ATP, a classical P2X‐type receptor mediating smooth muscle contraction, and a P2Y (G‐protein linked) receptor mediating smooth muscle relaxation. The results also indicate that the ATP‐evoked relaxation may occur through the activation of cyclicAMP‐dependent PKA.
British Journal of Pharmacology (1998) 123, 1579–1586; doi:10.1038/sj.bjp.0701774</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>9605564</pmid><doi>10.1038/sj.bjp.0701774</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adenosine Diphosphate - pharmacology Adenosine Triphosphate - analogs & derivatives Adenosine Triphosphate - pharmacology Adenosinic and purinergic receptors Animals ATP Biological and medical sciences Callithrix Cell receptors Cell structures and functions cibacron blue 3GA cyclicAMP Female Fundamental and applied biological sciences. Psychology In Vitro Techniques Male marmoset urinary bladder Molecular and cellular biology Muscle Contraction - drug effects Muscle Contraction - physiology Muscle Relaxation - drug effects Muscle Relaxation - physiology Muscle, Smooth - drug effects Muscle, Smooth - innervation Muscle, Smooth - physiology P2 receptors Receptors, Purinergic - drug effects Receptors, Purinergic P1 - drug effects Receptors, Purinergic P2 - drug effects smooth muscle contraction and relaxation suramin Urinary Bladder - drug effects Urinary Bladder - innervation Urinary Bladder - physiology |
title | Purinoceptor subtypes mediating contraction and relaxation of marmoset urinary bladder smooth muscle |
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