{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T17:27:27Z","timestamp":1787246847719,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":2131,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2003,4,1]],"date-time":"2003-04-01T00:00:00Z","timestamp":1049155200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2003,4]]},"abstract":"<jats:p>\n                    <jats:list list-type=\"explicit-label\">\n                      <jats:list-item>\n                        <jats:p>\n                          Muscarinic agonist specificity is limited, making it difficult to match receptor subtypes with signal transduction cascades that mediate ion channel modulation. We have characterized the inhibitory effects of two muscarinic agonists, oxotremorine\u2010M (Oxo\u2010M) and bethanechol chloride (BeCh), on Ca\n                          <jats:sup>2+<\/jats:sup>\n                          currents in neonatal rat superior cervical ganglion neurons.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Oxo\u2010M\u2010mediated (10\n                          <jats:italic>\u03bc<\/jats:italic>\n                          <jats:sc>M<\/jats:sc>\n                          ) inhibition occurred\n                          <jats:italic>via<\/jats:italic>\n                          two signaling pathways. The first pathway inhibited whole cell peak currents, consisting primarily of N\u2010type current, but not FPL 64176\u2010induced, long\u2010lasting tail currents, comprised entirely of L\u2010type current. Inhibited currents displayed slowed activation kinetics and voltage dependence, characteristics of membrane\u2010delimited inhibition. Current inhibition was blocked by the selective M\n                          <jats:sub>2<\/jats:sub>\n                          receptor antagonist, methoctramine (METH; 100 n\n                          <jats:sc>M<\/jats:sc>\n                          ), or following pertussis toxin (PTX) pretreatment.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Activation of the second pathway inhibited both peak and long\u2010lasting tail currents. This pathway was voltage\u2010independent, PTX\u2010insensitive, but sensitive to internal Ca\n                          <jats:sup>2+<\/jats:sup>\n                          chelator concentration. Muscarinic toxin 7 (MT\u20107, 100 n\n                          <jats:sc>M<\/jats:sc>\n                          ), an irreversible M\n                          <jats:sub>1<\/jats:sub>\n                          receptor antagonist, eliminated this inhibition. Oxo\u2010M (100\n                          <jats:italic>\u03bc<\/jats:italic>\n                          <jats:sc>M<\/jats:sc>\n                          ) decreased L\u2010 and N\u2010type channel activities in cell\u2010attached patches, indicating that a diffusible second messenger is involved.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          BeCh (100\n                          <jats:italic>\u03bc<\/jats:italic>\n                          <jats:sc>M<\/jats:sc>\n                          ) also inhibited whole cell currents\n                          <jats:italic>via<\/jats:italic>\n                          the membrane\u2010delimited pathway. Blocking M\n                          <jats:sub>4<\/jats:sub>\n                          receptors with 100 n\n                          <jats:sc>M<\/jats:sc>\n                          pirenzepine (in the presence of MT\u20107) had no effect, while antagonizing M\n                          <jats:sub>2<\/jats:sub>\n                          receptors with METH abolished inhibition. Concentrations of BeCh as high as 3 m\n                          <jats:sc>M<\/jats:sc>\n                          failed to inhibit either peak or long\u2010lasting tail currents following PTX pretreatment.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          These results indicate that BeCh may be an effective tool for selectively activating M\n                          <jats:sub>2<\/jats:sub>\n                          receptor stimulation of the membrane\u2010delimited pathway.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>British Journal of Pharmacology<\/jats:italic>\n                    (2003)\n                    <jats:bold>138<\/jats:bold>\n                    , 1259\u20131270. doi:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705157\">10.1038\/sj.bjp.0705157<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1038\/sj.bjp.0705157","type":"journal-article","created":{"date-parts":[[2003,4,23]],"date-time":"2003-04-23T16:34:36Z","timestamp":1051115676000},"page":"1259-1270","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Pharmacological discrimination between muscarinic receptor signal transduction cascades with bethanechol chloride"],"prefix":"10.1111","volume":"138","author":[{"given":"Liwang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann R","family":"Rittenhouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(97)00049-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019715"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/340153a0"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90111-P"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.2.652"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90226-P"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.20.9544"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-12-04646.1988"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0026-895X(25)11261-3","article-title":"Antagonist binding properties of five cloned muscarinic receptors expressed in CHO\u201011 cells","volume":"35","author":"BUCKLEY N.J.","year":"1989","journal-title":"Mol. 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