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The modified oil\u2010immersion method by Kalsner and Nickerson was used to record time profiles after cessation of a steady state myometrium contraction triggered by analogues in a high potassium tissue medium. An exchange of the aqueous medium for mineral oil enables to suppress return diffusion of the peptide and to record its irreversible clearance near the corresponding receptor compartment. Response records were analysed by a nonlinear numeric procedure based on combination of steady state and kinetic terms that allows concomitant estimations of affinities from time\u2013response measurements, in the given case for analogues on depolarized myometrium. Potential inactivation\u2010sensitive sites in the oxytocin chain are the <jats:italic>\u039d<\/jats:italic>\u2010terminal peptide bond Cys<jats:sup>1<\/jats:sup>\u2010Tyr<jats:sup>2<\/jats:sup> (aminopeptidase splitting), the intramolecular disulphide bridge (reduction and formation of the practically inactive linear peptide) and the <jats:italic>C\u2010<\/jats:italic>terminal Leu<jats:sup>8<\/jats:sup>\u2010GlyNH<jats:sub>2<\/jats:sub><jats:sup>9<\/jats:sup> or the Pro<jats:sup>7<\/jats:sup>\u2010Leu<jats:sup>8<\/jats:sup> (postprolin cleaving enzyme) bond, respectively. Clearance rate constants of single peptides in the OXT\u2010receptor compartment were in an interval of 0.025 to 0.28\u2009min<jats:sup>\u22121<\/jats:sup>. The fragment contribution analysis reveals a significant linear additivity of individual structural changes and thus a predictivity of irreversible inactivation rate in the receptor compartment. The most potent inactivation of oxytocin is associated with aminopeptidase splitting; other enzymes may play some though nondecisive role. Less significant differences within the peptide group were found for rate constants for peptide transport between receptor compartment and its external aqueous medium. Besides rate constants, the evaluation of time\u2013response data yields affinity values of the tested peptides and indicates a 25\u2010times desensitation of depolarized compared with a native state.<\/jats:p>","DOI":"10.1002\/psc.3372","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T21:11:47Z","timestamp":1634677907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clearance of oxytocin and its potentially enzyme resistant analogues in the <i>OXT<\/i>\u2010receptor compartment of the potassium depolarized rat myometrium"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3018-5742","authenticated-orcid":false,"given":"Vladimir","family":"Pliska","sequence":"first","affiliation":[{"name":"Department of Biology Swiss Federal Institute of Technology (ETH)  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Jutz","sequence":"additional","affiliation":[{"name":"Department of Biology Swiss Federal Institute of Technology (ETH)  Z\u00fcrich Switzerland"},{"name":"Department of Molecular Biology and Biophysics Swiss Federal Institute of Technology  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-46127-9_6"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1959.tb00252.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(69)90146-0"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(74)90095-8"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1135\/cccc19812441"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-158-40269"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-106-3-805"},{"key":"e_1_2_9_9_1","first-page":"325","article-title":"Third international standard for posterior pituitary (re\u2010named third international standard for oxytocic, vasopressor and antidiuretic substances in 1956)","volume":"19","author":"Bangham DR","year":"1958","journal-title":"Bull Wld Hlth Org"},{"issue":"7","key":"e_1_2_9_10_1","first-page":"886","article-title":"On the in vivo kinetics of drug action","volume":"16","author":"Pli\u0161ka V","year":"1966","journal-title":"Arzneim\u2010Forsch"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1976.tb03817.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3011.1979.tb01902.x"},{"key":"e_1_2_9_13_1","first-page":"131","article-title":"Oxytocin analogs in the analysis of some phases of hormone action","volume":"28","author":"Rudinger J","year":"1972","journal-title":"Rec Prog Hormone Res"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(68)90904-5"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(77)91197-7"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2044.2004.03877.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1135\/cccc19741271"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1805489"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(99)70271-1"},{"key":"e_1_2_9_20_1","first-page":"623","article-title":"Pharmacokinetics of neurohypophysial and related peptides: Mathematical models","volume":"23","author":"Pli\u0161ka V","year":"1968","journal-title":"Il Farmaco, Ed Sci"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-08-003265-8.50009-7"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00177709"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2018.01.006"},{"key":"e_1_2_9_24_1","first-page":"14","volume-title":"Pharmacologic Analysis of Drug\u2010Receptor Interaction","author":"Kenakin TP","year":"1993"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-08-003265-8.50005-X"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1139\/y68-113"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1969.tb08281.x"},{"key":"e_1_2_9_28_1","first-page":"603","volume-title":"Peptides: Structure and Function. 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