Heterogeneity of muscarinic receptors coupled to phosphoinositide breakdown in guinea pig brain and peripheral tissues
Muscarinic receptors coupled to phosphoinositide hydrolysis (PI) are present in guinea pig bladder and colon. Compared to rat cerebral cortex, an extensively studied muscarinic/PI turnover system, all agonists were more potent and efficacious in both bladder and colon. The “M 1-selective antagonists...
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| Veröffentlicht in: | Life sciences (1973) 1987-08, Vol.41 (8), p.967-975 |
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| container_title | Life sciences (1973) |
| container_volume | 41 |
| creator | Noronha-Blob, L. Lowe, V.C. Hanson, R.C. U'Prichard, D.C. |
| description | Muscarinic receptors coupled to phosphoinositide hydrolysis (PI) are present in guinea pig bladder and colon. Compared to rat cerebral cortex, an extensively studied muscarinic/PI turnover system, all agonists were more potent and efficacious in both bladder and colon. The “M
1-selective antagonists”, pirenzepine and dicyclomine, were much more potent (K
i = 1−5 nM) and selective (300 to 500-fold) at both rat and guinea pig brain and guinea pig colon receptors, compared to PI-coupled receptors in guinea pig bladder. In contrast, “M
2-selective antagonists”, AF-DX 116 and HHSiD, were 2–6 fold more potent in bladder than in brain, while HHSiD was very potent in the colon (50 times more potent than in brain). These results suggest a pharmacological heterogeneity of PI-linked muscarinic receptors. If muscarinic receptors with a low affinity for pirenzepine are defined as M
2, these results show that the guinea pig bladder contains PI-linked M
2 muscarinic receptors, whereas the guinea pig colon contains PI-linked M
1 receptors. |
| doi_str_mv | 10.1016/0024-3205(87)90684-9 |
| format | Article |
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1-selective antagonists”, pirenzepine and dicyclomine, were much more potent (K
i = 1−5 nM) and selective (300 to 500-fold) at both rat and guinea pig brain and guinea pig colon receptors, compared to PI-coupled receptors in guinea pig bladder. In contrast, “M
2-selective antagonists”, AF-DX 116 and HHSiD, were 2–6 fold more potent in bladder than in brain, while HHSiD was very potent in the colon (50 times more potent than in brain). These results suggest a pharmacological heterogeneity of PI-linked muscarinic receptors. If muscarinic receptors with a low affinity for pirenzepine are defined as M
2, these results show that the guinea pig bladder contains PI-linked M
2 muscarinic receptors, whereas the guinea pig colon contains PI-linked M
1 receptors.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/0024-3205(87)90684-9</identifier><identifier>PMID: 3039279</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>acetylcholine ; Animals ; brain ; Cerebral Cortex - metabolism ; Colon - metabolism ; Guinea Pigs ; Male ; Parasympatholytics - classification ; Parasympatholytics - pharmacology ; Parasympathomimetics - classification ; Parasympathomimetics - pharmacology ; Phosphatidylinositols - metabolism ; phosphoinositides ; Rats ; Rats, Inbred Strains ; Receptors, Muscarinic - classification ; Receptors, Muscarinic - drug effects ; Receptors, Muscarinic - metabolism ; Urinary Bladder - metabolism</subject><ispartof>Life sciences (1973), 1987-08, Vol.41 (8), p.967-975</ispartof><rights>1987</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-8dd86104b28f1d0656a82aee02345a7ca0d66da7db32c8fe0b4b9301fd8862ce3</citedby><cites>FETCH-LOGICAL-c454t-8dd86104b28f1d0656a82aee02345a7ca0d66da7db32c8fe0b4b9301fd8862ce3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/0024320587906849$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3039279$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Noronha-Blob, L.</creatorcontrib><creatorcontrib>Lowe, V.C.</creatorcontrib><creatorcontrib>Hanson, R.C.</creatorcontrib><creatorcontrib>U'Prichard, D.C.</creatorcontrib><title>Heterogeneity of muscarinic receptors coupled to phosphoinositide breakdown in guinea pig brain and peripheral tissues</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>Muscarinic receptors coupled to phosphoinositide hydrolysis (PI) are present in guinea pig bladder and colon. Compared to rat cerebral cortex, an extensively studied muscarinic/PI turnover system, all agonists were more potent and efficacious in both bladder and colon. The “M
1-selective antagonists”, pirenzepine and dicyclomine, were much more potent (K
i = 1−5 nM) and selective (300 to 500-fold) at both rat and guinea pig brain and guinea pig colon receptors, compared to PI-coupled receptors in guinea pig bladder. In contrast, “M
2-selective antagonists”, AF-DX 116 and HHSiD, were 2–6 fold more potent in bladder than in brain, while HHSiD was very potent in the colon (50 times more potent than in brain). These results suggest a pharmacological heterogeneity of PI-linked muscarinic receptors. If muscarinic receptors with a low affinity for pirenzepine are defined as M
2, these results show that the guinea pig bladder contains PI-linked M
2 muscarinic receptors, whereas the guinea pig colon contains PI-linked M
1 receptors.</description><subject>acetylcholine</subject><subject>Animals</subject><subject>brain</subject><subject>Cerebral Cortex - metabolism</subject><subject>Colon - metabolism</subject><subject>Guinea Pigs</subject><subject>Male</subject><subject>Parasympatholytics - classification</subject><subject>Parasympatholytics - pharmacology</subject><subject>Parasympathomimetics - classification</subject><subject>Parasympathomimetics - pharmacology</subject><subject>Phosphatidylinositols - metabolism</subject><subject>phosphoinositides</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Receptors, Muscarinic - classification</subject><subject>Receptors, Muscarinic - drug effects</subject><subject>Receptors, Muscarinic - metabolism</subject><subject>Urinary Bladder - metabolism</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1987</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1v1DAUtBCobAv_ACSfED2EPn_Edi5IVQUUqVIv5Ww59svWkLWDnRT13zfLrnqEw9OT3sy8kWYIecfgEwOmLgC4bASH9qPR5x0oI5vuBdkwo7sGlGAvyeaZ8pqc1voTANpWixNyIkB0XHcb8nCNM5a8xYRxfqR5oLuleldiip4W9DjNuVTq8zKNGOic6XSf6zox5RrnGJD2Bd2vkP8kGhPdLjGho1Pcrne3HlwKdMISp3ssbqRzrHXB-oa8GtxY8e1xn5EfX7_cXV03N7ffvl9d3jRetnJuTAhGMZA9NwMLoFrlDHeIwIVsnfYOglLB6dAL7s2A0Mu-E8CGYIziHsUZ-XD4O5X8e_Wd7S5Wj-PoEualWq0VB67lf4lM6lYxpleiPBB9ybUWHOxU4s6VR8vA7nux-9DtPnRrtP3bi-1W2fvj_6XfYXgWHYtY8c8HHNc0HiIWW33E5DHEtYXZhhz_bfAEcmWfNg</recordid><startdate>19870824</startdate><enddate>19870824</enddate><creator>Noronha-Blob, L.</creator><creator>Lowe, V.C.</creator><creator>Hanson, R.C.</creator><creator>U'Prichard, D.C.</creator><general>Elsevier Inc</general><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>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19870824</creationdate><title>Heterogeneity of muscarinic receptors coupled to phosphoinositide breakdown in guinea pig brain and peripheral tissues</title><author>Noronha-Blob, L. ; Lowe, V.C. ; Hanson, R.C. ; U'Prichard, D.C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-8dd86104b28f1d0656a82aee02345a7ca0d66da7db32c8fe0b4b9301fd8862ce3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1987</creationdate><topic>acetylcholine</topic><topic>Animals</topic><topic>brain</topic><topic>Cerebral Cortex - metabolism</topic><topic>Colon - metabolism</topic><topic>Guinea Pigs</topic><topic>Male</topic><topic>Parasympatholytics - classification</topic><topic>Parasympatholytics - pharmacology</topic><topic>Parasympathomimetics - classification</topic><topic>Parasympathomimetics - pharmacology</topic><topic>Phosphatidylinositols - metabolism</topic><topic>phosphoinositides</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Receptors, Muscarinic - classification</topic><topic>Receptors, Muscarinic - drug effects</topic><topic>Receptors, Muscarinic - metabolism</topic><topic>Urinary Bladder - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Noronha-Blob, L.</creatorcontrib><creatorcontrib>Lowe, V.C.</creatorcontrib><creatorcontrib>Hanson, R.C.</creatorcontrib><creatorcontrib>U'Prichard, D.C.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Noronha-Blob, L.</au><au>Lowe, V.C.</au><au>Hanson, R.C.</au><au>U'Prichard, D.C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Heterogeneity of muscarinic receptors coupled to phosphoinositide breakdown in guinea pig brain and peripheral tissues</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>1987-08-24</date><risdate>1987</risdate><volume>41</volume><issue>8</issue><spage>967</spage><epage>975</epage><pages>967-975</pages><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>Muscarinic receptors coupled to phosphoinositide hydrolysis (PI) are present in guinea pig bladder and colon. Compared to rat cerebral cortex, an extensively studied muscarinic/PI turnover system, all agonists were more potent and efficacious in both bladder and colon. The “M
1-selective antagonists”, pirenzepine and dicyclomine, were much more potent (K
i = 1−5 nM) and selective (300 to 500-fold) at both rat and guinea pig brain and guinea pig colon receptors, compared to PI-coupled receptors in guinea pig bladder. In contrast, “M
2-selective antagonists”, AF-DX 116 and HHSiD, were 2–6 fold more potent in bladder than in brain, while HHSiD was very potent in the colon (50 times more potent than in brain). These results suggest a pharmacological heterogeneity of PI-linked muscarinic receptors. If muscarinic receptors with a low affinity for pirenzepine are defined as M
2, these results show that the guinea pig bladder contains PI-linked M
2 muscarinic receptors, whereas the guinea pig colon contains PI-linked M
1 receptors.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>3039279</pmid><doi>10.1016/0024-3205(87)90684-9</doi><tpages>9</tpages></addata></record> |
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| ispartof | Life sciences (1973), 1987-08, Vol.41 (8), p.967-975 |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | acetylcholine Animals brain Cerebral Cortex - metabolism Colon - metabolism Guinea Pigs Male Parasympatholytics - classification Parasympatholytics - pharmacology Parasympathomimetics - classification Parasympathomimetics - pharmacology Phosphatidylinositols - metabolism phosphoinositides Rats Rats, Inbred Strains Receptors, Muscarinic - classification Receptors, Muscarinic - drug effects Receptors, Muscarinic - metabolism Urinary Bladder - metabolism |
| title | Heterogeneity of muscarinic receptors coupled to phosphoinositide breakdown in guinea pig brain and peripheral tissues |
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