Interaction of pinaverium (a quaternary ammonium compound) with 1,4‐dihydropyridine binding sites in rat ileum smooth muscle
1 The interaction of pinaverium bromide, a quaternary ammonium compound, with binding sites for (L‐type) calcium channel blockers was investigated in rat ileum smooth muscle. 2 Pinaverium inhibited [3H]‐(+)‐PN200–110 ([3H]‐(+)‐isradipine) specific binding to tissue homogenates incompletely (Ki 0.38...
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| Veröffentlicht in: | British journal of pharmacology 1992-02, Vol.105 (2), p.480-484 |
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| creator | Feron, Olivier Wibo, Maurice Christen, Marie‐Odile Godfraind, Théophile |
| description | 1
The interaction of pinaverium bromide, a quaternary ammonium compound, with binding sites for (L‐type) calcium channel blockers was investigated in rat ileum smooth muscle.
2
Pinaverium inhibited [3H]‐(+)‐PN200–110 ([3H]‐(+)‐isradipine) specific binding to tissue homogenates incompletely (Ki 0.38 μm; maximal inhibition 80%). In contrast, binding to single cell preparations (obtained by collagenase treatment) and to saponin‐treated homogenates was completely inhibited. These data are compatible with the view that, in untreated homogenates, 20% of [3H]‐(+)‐isradipine binding sites are not accessible to pinaverium because it is associated with sealed inside‐out vesicles.
3
Pinaverium bromide increased the apparent KD of [3H]‐(+)‐isradipine binding to saponin‐treated homogenates but did not significantly affect the Bmax value. Moreover, the dissociation rate constant of [3H]‐(+)‐isradipine binding was not changed by pinaverium. These data suggest that pinaverium interacts with the dihydropyridine binding site in a competitive manner. However, in contrast to uncharged dihydropyridine calcium antagonists, pinaverium inhibited, rather than stimulated, [3H]‐diltiazem binding to rat brain membranes (at 30–37°C).
4
Although Bmax values of [3H]‐(+)‐isradipine were similar in homogenates prepared from tissue and cells (collagenase‐treated), the KD value was significantly higher in cell homogenates (166 vs 95 pm). Similarly, the Ki value of pinaverium was higher in cell preparations than in tissue homogenates (0.77 vs 0.38 μm). Thus, collagenase can significantly modify the dihydropyridine recognition site.
5
The competitive interaction of pinaverium, a permanently charged drug, with [3H]‐(+)‐isradipine bound to intact cells and its absence of interaction with [3H]‐(+)‐isradipine bound to sealed inside‐out vesicles imply that the dihydropyridine receptor lies near the external surface of the plasma membrane. |
| doi_str_mv | 10.1111/j.1476-5381.1992.tb14279.x |
| format | Article |
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The interaction of pinaverium bromide, a quaternary ammonium compound, with binding sites for (L‐type) calcium channel blockers was investigated in rat ileum smooth muscle.
2
Pinaverium inhibited [3H]‐(+)‐PN200–110 ([3H]‐(+)‐isradipine) specific binding to tissue homogenates incompletely (Ki 0.38 μm; maximal inhibition 80%). In contrast, binding to single cell preparations (obtained by collagenase treatment) and to saponin‐treated homogenates was completely inhibited. These data are compatible with the view that, in untreated homogenates, 20% of [3H]‐(+)‐isradipine binding sites are not accessible to pinaverium because it is associated with sealed inside‐out vesicles.
3
Pinaverium bromide increased the apparent KD of [3H]‐(+)‐isradipine binding to saponin‐treated homogenates but did not significantly affect the Bmax value. Moreover, the dissociation rate constant of [3H]‐(+)‐isradipine binding was not changed by pinaverium. These data suggest that pinaverium interacts with the dihydropyridine binding site in a competitive manner. However, in contrast to uncharged dihydropyridine calcium antagonists, pinaverium inhibited, rather than stimulated, [3H]‐diltiazem binding to rat brain membranes (at 30–37°C).
4
Although Bmax values of [3H]‐(+)‐isradipine were similar in homogenates prepared from tissue and cells (collagenase‐treated), the KD value was significantly higher in cell homogenates (166 vs 95 pm). Similarly, the Ki value of pinaverium was higher in cell preparations than in tissue homogenates (0.77 vs 0.38 μm). Thus, collagenase can significantly modify the dihydropyridine recognition site.
5
The competitive interaction of pinaverium, a permanently charged drug, with [3H]‐(+)‐isradipine bound to intact cells and its absence of interaction with [3H]‐(+)‐isradipine bound to sealed inside‐out vesicles imply that the dihydropyridine receptor lies near the external surface of the plasma membrane.</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1111/j.1476-5381.1992.tb14279.x</identifier><identifier>PMID: 1313732</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; Binding Sites ; Binding, Competitive - drug effects ; Biological and medical sciences ; calcium ; Calcium Channel Blockers - pharmacology ; Calcium Channels ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; channels ; collagenase ; dihydropyridine Ca2+ antagonists ; Dihydropyridines - metabolism ; Dihydropyridines - pharmacology ; diltiazem ; Diltiazem - pharmacokinetics ; ileum ; Ileum - drug effects ; Ileum - metabolism ; ileum smooth muscle ; In Vitro Techniques ; interaction ; Isradipine ; Kinetics ; Medical sciences ; Morpholines - pharmacology ; Muscle ; Muscle, Smooth - drug effects ; Muscle, Smooth - metabolism ; Parasympatholytics - pharmacology ; Pharmacology. Drug treatments ; pinaverium ; Pinaverium bromide ; Rats ; Receptors, Nicotinic - drug effects ; Receptors, Nicotinic - metabolism ; Saponins - pharmacokinetics ; smooth muscle</subject><ispartof>British journal of pharmacology, 1992-02, Vol.105 (2), p.480-484</ispartof><rights>1992 British Pharmacological Society</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5389-ea638a5ef460196f258d0c75aceec306ef72ff4fe26c0581a2f9f6da5333972a3</citedby><cites>FETCH-LOGICAL-c5389-ea638a5ef460196f258d0c75aceec306ef72ff4fe26c0581a2f9f6da5333972a3</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/PMC1908673/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1908673/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5192731$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1313732$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Feron, Olivier</creatorcontrib><creatorcontrib>Wibo, Maurice</creatorcontrib><creatorcontrib>Christen, Marie‐Odile</creatorcontrib><creatorcontrib>Godfraind, Théophile</creatorcontrib><title>Interaction of pinaverium (a quaternary ammonium compound) with 1,4‐dihydropyridine binding sites in rat ileum smooth muscle</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>1
The interaction of pinaverium bromide, a quaternary ammonium compound, with binding sites for (L‐type) calcium channel blockers was investigated in rat ileum smooth muscle.
2
Pinaverium inhibited [3H]‐(+)‐PN200–110 ([3H]‐(+)‐isradipine) specific binding to tissue homogenates incompletely (Ki 0.38 μm; maximal inhibition 80%). In contrast, binding to single cell preparations (obtained by collagenase treatment) and to saponin‐treated homogenates was completely inhibited. These data are compatible with the view that, in untreated homogenates, 20% of [3H]‐(+)‐isradipine binding sites are not accessible to pinaverium because it is associated with sealed inside‐out vesicles.
3
Pinaverium bromide increased the apparent KD of [3H]‐(+)‐isradipine binding to saponin‐treated homogenates but did not significantly affect the Bmax value. Moreover, the dissociation rate constant of [3H]‐(+)‐isradipine binding was not changed by pinaverium. These data suggest that pinaverium interacts with the dihydropyridine binding site in a competitive manner. However, in contrast to uncharged dihydropyridine calcium antagonists, pinaverium inhibited, rather than stimulated, [3H]‐diltiazem binding to rat brain membranes (at 30–37°C).
4
Although Bmax values of [3H]‐(+)‐isradipine were similar in homogenates prepared from tissue and cells (collagenase‐treated), the KD value was significantly higher in cell homogenates (166 vs 95 pm). Similarly, the Ki value of pinaverium was higher in cell preparations than in tissue homogenates (0.77 vs 0.38 μm). Thus, collagenase can significantly modify the dihydropyridine recognition site.
5
The competitive interaction of pinaverium, a permanently charged drug, with [3H]‐(+)‐isradipine bound to intact cells and its absence of interaction with [3H]‐(+)‐isradipine bound to sealed inside‐out vesicles imply that the dihydropyridine receptor lies near the external surface of the plasma membrane.</description><subject>Animals</subject><subject>Binding Sites</subject><subject>Binding, Competitive - drug effects</subject><subject>Biological and medical sciences</subject><subject>calcium</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Calcium Channels</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane - metabolism</subject><subject>channels</subject><subject>collagenase</subject><subject>dihydropyridine Ca2+ antagonists</subject><subject>Dihydropyridines - metabolism</subject><subject>Dihydropyridines - pharmacology</subject><subject>diltiazem</subject><subject>Diltiazem - pharmacokinetics</subject><subject>ileum</subject><subject>Ileum - drug effects</subject><subject>Ileum - metabolism</subject><subject>ileum smooth muscle</subject><subject>In Vitro Techniques</subject><subject>interaction</subject><subject>Isradipine</subject><subject>Kinetics</subject><subject>Medical sciences</subject><subject>Morpholines - pharmacology</subject><subject>Muscle</subject><subject>Muscle, Smooth - drug effects</subject><subject>Muscle, Smooth - metabolism</subject><subject>Parasympatholytics - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>pinaverium</subject><subject>Pinaverium bromide</subject><subject>Rats</subject><subject>Receptors, Nicotinic - drug effects</subject><subject>Receptors, Nicotinic - metabolism</subject><subject>Saponins - pharmacokinetics</subject><subject>smooth muscle</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkd-K1DAYxYMo6-zoIwhBRFawNX_apvVC1EXdhQW90OvwTZrsZGiTbtLu7tyIj-Az-iSmzjDqlZibhJxzPr7DD6HHlOQ0nRebnBaiykpe05w2DcvHFS2YaPLbO2hxkO6iBSFEZJTW9X10HOOGkCSK8ggdUU654GyBvp67UQdQo_UOe4MH6-BaBzv1-ATw1QRJdRC2GPreu_lb-X7wk2uf4Rs7rjF9Xvz49r21620b_LANtrVO45V16b7E0Y46YutwgBHbTqd87L1PuX6KqtMP0D0DXdQP9_cSfXn_7vPpWXbx8cP56ZuLTKUmTaah4jWU2hQVoU1lWFm3RIkSlNaKk0obwYwpjGaVImVNgZnGVC2UnPNGMOBL9Go3d5hWvW6VdmOATg7B9qmc9GDl34qza3npryVtSF0JngY83Q8I_mrScZS9jUp3HTjtpygFq0XNyb-NNDUpKGfJ-HJnVMHHGLQ5bEOJnDHLjZxZypmlnDHLPWZ5m8KP_uzzO7rjmvQnex2igs4EcMrGg62kDRPJukSvd7abxGb7HwvIt5_Ofj35T12CybU</recordid><startdate>199202</startdate><enddate>199202</enddate><creator>Feron, Olivier</creator><creator>Wibo, Maurice</creator><creator>Christen, Marie‐Odile</creator><creator>Godfraind, Théophile</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>7QP</scope><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>199202</creationdate><title>Interaction of pinaverium (a quaternary ammonium compound) with 1,4‐dihydropyridine binding sites in rat ileum smooth muscle</title><author>Feron, Olivier ; Wibo, Maurice ; Christen, Marie‐Odile ; Godfraind, Théophile</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5389-ea638a5ef460196f258d0c75aceec306ef72ff4fe26c0581a2f9f6da5333972a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Animals</topic><topic>Binding Sites</topic><topic>Binding, Competitive - drug effects</topic><topic>Biological and medical sciences</topic><topic>calcium</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Calcium Channels</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - metabolism</topic><topic>channels</topic><topic>collagenase</topic><topic>dihydropyridine Ca2+ antagonists</topic><topic>Dihydropyridines - metabolism</topic><topic>Dihydropyridines - pharmacology</topic><topic>diltiazem</topic><topic>Diltiazem - pharmacokinetics</topic><topic>ileum</topic><topic>Ileum - drug effects</topic><topic>Ileum - metabolism</topic><topic>ileum smooth muscle</topic><topic>In Vitro Techniques</topic><topic>interaction</topic><topic>Isradipine</topic><topic>Kinetics</topic><topic>Medical sciences</topic><topic>Morpholines - pharmacology</topic><topic>Muscle</topic><topic>Muscle, Smooth - drug effects</topic><topic>Muscle, Smooth - metabolism</topic><topic>Parasympatholytics - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>pinaverium</topic><topic>Pinaverium bromide</topic><topic>Rats</topic><topic>Receptors, Nicotinic - drug effects</topic><topic>Receptors, Nicotinic - metabolism</topic><topic>Saponins - pharmacokinetics</topic><topic>smooth muscle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Feron, Olivier</creatorcontrib><creatorcontrib>Wibo, Maurice</creatorcontrib><creatorcontrib>Christen, Marie‐Odile</creatorcontrib><creatorcontrib>Godfraind, Théophile</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>Calcium & Calcified Tissue 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><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>Feron, Olivier</au><au>Wibo, Maurice</au><au>Christen, Marie‐Odile</au><au>Godfraind, Théophile</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interaction of pinaverium (a quaternary ammonium compound) with 1,4‐dihydropyridine binding sites in rat ileum smooth muscle</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>1992-02</date><risdate>1992</risdate><volume>105</volume><issue>2</issue><spage>480</spage><epage>484</epage><pages>480-484</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>1
The interaction of pinaverium bromide, a quaternary ammonium compound, with binding sites for (L‐type) calcium channel blockers was investigated in rat ileum smooth muscle.
2
Pinaverium inhibited [3H]‐(+)‐PN200–110 ([3H]‐(+)‐isradipine) specific binding to tissue homogenates incompletely (Ki 0.38 μm; maximal inhibition 80%). In contrast, binding to single cell preparations (obtained by collagenase treatment) and to saponin‐treated homogenates was completely inhibited. These data are compatible with the view that, in untreated homogenates, 20% of [3H]‐(+)‐isradipine binding sites are not accessible to pinaverium because it is associated with sealed inside‐out vesicles.
3
Pinaverium bromide increased the apparent KD of [3H]‐(+)‐isradipine binding to saponin‐treated homogenates but did not significantly affect the Bmax value. Moreover, the dissociation rate constant of [3H]‐(+)‐isradipine binding was not changed by pinaverium. These data suggest that pinaverium interacts with the dihydropyridine binding site in a competitive manner. However, in contrast to uncharged dihydropyridine calcium antagonists, pinaverium inhibited, rather than stimulated, [3H]‐diltiazem binding to rat brain membranes (at 30–37°C).
4
Although Bmax values of [3H]‐(+)‐isradipine were similar in homogenates prepared from tissue and cells (collagenase‐treated), the KD value was significantly higher in cell homogenates (166 vs 95 pm). Similarly, the Ki value of pinaverium was higher in cell preparations than in tissue homogenates (0.77 vs 0.38 μm). Thus, collagenase can significantly modify the dihydropyridine recognition site.
5
The competitive interaction of pinaverium, a permanently charged drug, with [3H]‐(+)‐isradipine bound to intact cells and its absence of interaction with [3H]‐(+)‐isradipine bound to sealed inside‐out vesicles imply that the dihydropyridine receptor lies near the external surface of the plasma membrane.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>1313732</pmid><doi>10.1111/j.1476-5381.1992.tb14279.x</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of pharmacology, 1992-02, Vol.105 (2), p.480-484 |
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| subjects | Animals Binding Sites Binding, Competitive - drug effects Biological and medical sciences calcium Calcium Channel Blockers - pharmacology Calcium Channels Cell Membrane - drug effects Cell Membrane - metabolism channels collagenase dihydropyridine Ca2+ antagonists Dihydropyridines - metabolism Dihydropyridines - pharmacology diltiazem Diltiazem - pharmacokinetics ileum Ileum - drug effects Ileum - metabolism ileum smooth muscle In Vitro Techniques interaction Isradipine Kinetics Medical sciences Morpholines - pharmacology Muscle Muscle, Smooth - drug effects Muscle, Smooth - metabolism Parasympatholytics - pharmacology Pharmacology. Drug treatments pinaverium Pinaverium bromide Rats Receptors, Nicotinic - drug effects Receptors, Nicotinic - metabolism Saponins - pharmacokinetics smooth muscle |
| title | Interaction of pinaverium (a quaternary ammonium compound) with 1,4‐dihydropyridine binding sites in rat ileum smooth muscle |
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