{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T15:39:52Z","timestamp":1771515592418,"version":"3.50.1"},"reference-count":25,"publisher":"Walter de Gruyter GmbH","issue":"2","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R44DK112437"],"award-info":[{"award-number":["R44DK112437"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jbcpp-2022-0119_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Neurokinin 2 receptor (NK2R) agonists may be useful for treating bladder and bowel dysfunction via direct contraction of detrusor and gastrointestinal smooth muscle. The NK2R agonist [Lys5, MeLeu9, Nle10]-NKA(4\u201310) (LMN-NKA) induces urination and defecation, but also produces the potential side effect of dermal flushing in rats. Although LMN-NKA is a NK2R agonist, it\u00a0also has affinity for neurokinin 1 receptors (NK1R). Therefore, the goal of this study was to determine the neurokinin receptor (NKR) subtypes responsible for LMN-NKA-induced urination, defecation, and flushing by\u00a0blocking either NK2Rs or NK1Rs before LMN-NKA administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jbcpp-2022-0119_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To accomplish this goal, we developed a simple high-throughput \u2018rapid detection voiding assay\u2019 to detect rapid-onset drug-induced urination and defecation in rats. In LMN-NKA dose-response experiments, LMN-NKA (10\u2013100\u00a0\u03bcg\/kg, subcutaneous) was injected and urination, defecation, and flushing were monitored for 30\u00a0min. For NKR antagonist experiments, vehicle, the NK2R antagonist GR159897, or the NK1R antagonist CP-99,994 were injected before an acclimation period. Following acclimation, saline or 100\u00a0\u03bcg\/kg LMN-NKA were injected, and behavior was observed for 30\u00a0min.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jbcpp-2022-0119_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LMN-NKA produced dose-related increases in urination, defecation, and flushing. Blocking NK2Rs reduced urination and blocked defecation, without affecting flushing. Blocking NK1Rs did not change LMN-NKA-induced urination or defecation but reduced LMN-NKA-induced flushing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jbcpp-2022-0119_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Using the rapid detection voiding assay we show that LMN-NKA-induced urination and defecation are mediated by NK2Rs, while flushing is mediated by NK1Rs. Therefore, drugs that are more selective for NK2 vs. NK1Rs should produce rapid-onset urination and defecation without producing the potential side effect of flushing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jbcpp-2022-0119","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T09:14:20Z","timestamp":1668503660000},"page":"227-233","source":"Crossref","is-referenced-by-count":3,"title":["[Lys\n                    <sup>5<\/sup>\n                    ,MeLeu\n                    <sup>9<\/sup>\n                    ,Nle\n                    <sup>10<\/sup>\n                    ]-NKA\n                    <sub>(4\u201310)<\/sub>\n                    induces neurokinin 2 receptor mediated urination and defecation and neurokinin 1 receptor mediated flushing in rats: measured using the rapid detection voiding assay"],"prefix":"10.1515","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8048-9373","authenticated-orcid":false,"given":"Jason B.","family":"Cook","sequence":"first","affiliation":[{"name":"Dignify Therapeutics LLC , Research Triangle Park , NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond","family":"Piatt","sequence":"additional","affiliation":[{"name":"Dignify Therapeutics LLC , Research Triangle Park , NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lesley","family":"Marson","sequence":"additional","affiliation":[{"name":"Dignify Therapeutics LLC , Research Triangle Park , NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"2025121209054324439_j_jbcpp-2022-0119_ref_001","doi-asserted-by":"crossref","unstructured":"Singh, R, Rohilla, RK, Sangwan, K, Siwach, R, Magu, NK, Sangwan, SS. 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