{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:41:35Z","timestamp":1787067695742,"version":"build-2736575974"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK098361"],"award-info":[{"award-number":["R01DK098361"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:sec>\n                    <jats:title>New Findings<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:bold>What is the central question of this study?<\/jats:bold>\n                          <\/jats:p>\n                          <jats:p>Is the frequency dependence of co\u2010transmitter release from postganglionic nerve fibres different for each transmitter?<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:bold>What is the main finding and its importance?<\/jats:bold>\n                          <\/jats:p>\n                          <jats:p>Release of co\u2010transmitters from the parasympathetic supply to detrusor smooth muscle can be independently regulated. This offers a targeted drug model to reduce selectively the release of transmitter associated with human pathologies (ATP) and may also be applicable to other smooth muscle\u2010based disorders of visceral tissues.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Nerve\u2010mediated contractions of detrusor smooth muscle are mediated by acetylcholine (ACh) and ATP release in most animals. However, with the normal human bladder, only ACh is a functional transmitter, but in benign pathologies such as overactive bladder (OAB), ATP re\u2010emerges as a secondary transmitter. The selective regulation of ATP release offers a therapeutic approach to manage OAB, in contrast to current primary strategies that target ACh actions. However, the release characteristics of nerve\u2010mediated ACh and ATP are poorly defined and this study aimed to measure the frequency dependence of ACh and ATP release and determine if selective regulation of ATP or ACh was possible. Experiments were carried out in vitro with mouse detrusor with nerve\u2010mediated ATP and ACh release measured simultaneously with tension recording. ATP was released in two frequency\u2010dependent components, both at lower frequencies (mid\u2010range 0.4 and 5.5\u00a0Hz stimulation) compared to a single compartment release of ACh at 14\u00a0Hz. Intervention with the phosphodiesterase type\u20105 inhibitor sildenafil attenuated ATP release, equally from both components, but had no effect on ACh release. These data demonstrate that nerve\u2010mediated ACh and ATP release characteristics are distinct and may be separately manipulated. This offers a potential targeted drug model to manage benign lower urinary tract conditions such as OAB.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/ep090238","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T02:20:36Z","timestamp":1644891636000},"page":"350-358","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Frequency\u2010dependent characteristics of nerve\u2010mediated ATP and acetylcholine release from detrusor smooth muscle"],"prefix":"10.1113","volume":"107","author":[{"given":"Basu","family":"Chakrabarty","sequence":"first","affiliation":[{"name":"School of Physiology Pharmacology and Neuroscience University of Bristol  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Aitchison","sequence":"additional","affiliation":[{"name":"School of Physiology Pharmacology and Neuroscience University of Bristol  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"White","sequence":"additional","affiliation":[{"name":"Department of Engineering Design and Mathematics, Faculty of Environment and Technology University of West of England  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carly J.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones en Medicina Traslacional (IIMT) Facultad de Ciencias Biom\u00e9dicas Austral University  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Kanai","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3647-5983","authenticated-orcid":false,"given":"Christopher H.","family":"Fry","sequence":"additional","affiliation":[{"name":"School of Physiology Pharmacology and Neuroscience University of Bristol  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2010.00554.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)68247-X"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14669"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1976.sp011316"},{"key":"e_1_2_9_6_1","volume-title":"The Physiology of Nerve Cells","author":"Eccles J. 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