{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:01:29Z","timestamp":1790614889324,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,6,28]],"date-time":"2017-06-28T00:00:00Z","timestamp":1498608000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004823","name":"Nagoya University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004823","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Parathyroid hormone\u2010related protein (<jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>rP) that causes hypercalcemia of malignancy appears to function as an endogenous smooth muscle relaxant. For example, <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>rP released upon bladder wall distension relaxes detrusor smooth muscle to accommodate urine. Here, we explored mechanisms underlying <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>rP\u2010induced suppression of the smooth muscle contractility in the gastric antrum that also undergoes a passive distension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Effects of <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>rP on phasic contractions and electrical slow waves in the antral smooth muscle of the guinea pig stomach were studied using isometric tension and intracellular microelectrode recordings, respectively. Fluorescent immunohistochemistry was also carried out to identify the distribution of <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>rP receptors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Parathyroid hormone\u2010related protein (1\u2010100\u00a0nM) reduced the amplitude of phasic contractions and the basal tension. <jats:italic>N<\/jats:italic><jats:sup>\u03c9<\/jats:sup>\u2010nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine (L\u2010NA, 100\u00a0\u03bcM), a nitric oxide (<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>) synthase inhibitor, or 1H\u2010[1,2,4]oxadiazolo\u2010[4, 3\u2010a]quinoxalin\u20101\u2010one (ODQ, 10 \u00b5M), a guanylate cyclase inhibitor, diminished the <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>rP (10\u00a0nM)\u2010induced reduction in the amplitude of phasic contractions. SQ22536 (300\u00a0\u03bcM), an adenylate cyclase inhibitor, attenuated the <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>rP\u2010induced reduction in basal tension. The combination of ODQ (10\u00a0\u03bcM) and SQ22536 (300\u00a0\u03bcM) inhibited the <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>rP\u2010induced reductions in both phasic contractions and basal tension. <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>rP (100\u00a0nM) had no inhibitory effect on the electrical slow waves in the antral smooth muscle. <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>rP receptors were expressed in cell bodies of PGP9.5\u2010positive neurons in the myenteric plexus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Parathyroid hormone\u2010related protein exerts its inhibitory actions on the antral smooth muscle via both nitric oxide\u2010cyclic guanosine monophosphate (NO\u2010cGMP) and cyclic adenosine monophosphate (AMP) pathways. Thus, <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>rP may act as an endogenous relaxant of the gastric antrum employing the two complementary signaling pathways to ensure the adaptive relaxation of stomach.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13142","type":"journal-article","created":{"date-parts":[[2017,6,28]],"date-time":"2017-06-28T07:48:41Z","timestamp":1498636121000},"source":"Crossref","is-referenced-by-count":5,"title":["Mechanisms of PTHrP\u2010induced inhibition of smooth muscle contractility in the guinea pig gastric antrum"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1581-2039","authenticated-orcid":false,"given":"H.","family":"Ohguchi","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical Sciences  Nagoya Japan"},{"name":"Department of Cell Physiology Nagoya City University Graduate School of Medical Sciences  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Mitsui","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology Nagoya City University Graduate School of Medical Sciences  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Imaeda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical Sciences  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Joh","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical Sciences  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Hashitani","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology Nagoya City University Graduate School of Medical Sciences  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198012113032401"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.14.5048"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3616618"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(87)90581-X"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend-2-12-1230"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1996.76.1.127"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200001203420306"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.4.6740"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.133.2.8393771"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.12.5326"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-2142"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.18.6969"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650040319"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.134.4.8137762"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922-4106(94)90038-8"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(97)04044-6"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(97)00194-6"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00411.2004"},{"key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1210\/endo.135.5.7525262","article-title":"Parathyroid hormone (PTH) and PTH\u2010related peptide induce relaxation of smooth muscle cells from guinea pig ileum: interaction with vasoactive intestinal peptide receptors","volume":"135","author":"Botella A","year":"1994","journal-title":"Endocrinology"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.475"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/351477a0"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.24.11490"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.2170\/jjphysiol.51.693"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1540\/jsmr.45.109"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000420154"},{"key":"e_1_2_11_27_1","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1210\/endo.135.3.8070351","article-title":"Parathyroid hormone (PTH)\/PTH\u2010related protein (PTHrP) receptor and its messenger ribonucleic acid in rat aortic vascular smooth muscle cells and UMR osteoblast\u2010like cells: cell\u2010specific regulation by angiotensin\u2010II and PTHrP","volume":"135","author":"Okano K","year":"1994","journal-title":"Endocrinology"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020745"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1996.v111.pm8690216"},{"key":"e_1_2_11_30_1","first-page":"1435","article-title":"Electrical basis for gastrointestinal motility","volume":"2","author":"Szurszewski JH","year":"1981","journal-title":"Physiol Gastrointest Tract"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701487"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1658941"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704378"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.139"},{"key":"e_1_2_11_35_1","first-page":"G650","article-title":"Motility of the pyloric sphincter studied by the inductograph method in conscious dogs","volume":"254","author":"Ehrlein HJ","year":"1988","journal-title":"Am J Physiol"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnmo.13142","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.13142","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T10:13:00Z","timestamp":1696155180000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.13142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,28]]},"references-count":34,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1111\/nmo.13142"],"URL":"https:\/\/doi.org\/10.1111\/nmo.13142","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,28]]},"article-number":"e13142"}}