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R-phenylisopropyl adenosine (R-PIA) acts as an agonist at A<jats:sub>1<\/jats:sub>-adenosine receptors. R-PIA exerts a negative inotropic effect on human atria. The effect of R-PIA\u2014and its various manifestations\u2014are currently explained as a function of the inhibition of sarcolemmal adenylyl cyclase activity and\/or opening of sarcolemmal potassium channels. We hypothesise that cantharidin and sodium fluoride may attenuate the negative inotropic effect of R-PIA. During open heart surgery, trabeculae carneae from the right atrium were obtained for human atrial preparations (HAPs). These trabeculae were mounted in organ baths and electrically stimulated at 1\u00a0Hz. Furthermore, we studied isolated electrically stimulated left atrial (LA) preparations from female wild-type mice (CD1). The force of contraction was recorded under isometric conditions. R-PIA (1\u00a0\u00b5M) exerted a rapid negative inotropic effect in the HAPs and mice LA preparations. These negative inotropic effects of R-PIA were attenuated by pre-incubation for 30\u00a0min with 100-\u00b5M cantharidin in HAPs, but not in mice LA preparations. Adenosine signals via A<jats:sub>1<\/jats:sub> receptors in a species-specific pathway in mammalian atria. We postulate that R-PIA, at least in part, exerts a negative inotropic effect via activation of serine\/threonine phosphatases in the human atrium.<\/jats:p>","DOI":"10.1007\/s00210-024-03402-2","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T11:03:18Z","timestamp":1725015798000},"page":"1961-1971","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cantharidin and sodium fluoride attenuate the negative inotropic effect of the A1-adenosine receptor agonist N6-(R)-phenylisopropyl adenosine in isolated human atria"],"prefix":"10.1007","volume":"398","author":[{"given":"R.","family":"Schwarz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Gergs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,30]]},"reference":[{"issue":"7","key":"3402_CR1","doi-asserted-by":"publisher","first-page":"3859","DOI":"10.1016\/S0021-9258(19)84930-X","volume":"264","author":"Z Ahmad","year":"1989","unstructured":"Ahmad Z, Green FJ, Subuhi HS, Watanabe AM (1989) Autonomic regulation of type 1 protein phosphatase in cardiac muscle. 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The animals were handled and maintained according to the approved protocols of the Animal Welfare Committee of the University of Halle-Wittenberg, Halle, Germany. This study complies with the Declaration of Helsinki and was approved by a local ethics committee (hm-b\u00fc 04.08.2005).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed written consent was obtained from all patients recruited to the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors declare that they have seen and approved the version of this manuscript submitted for publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}