{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,22]],"date-time":"2023-10-22T13:14:07Z","timestamp":1697980447056},"reference-count":0,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[1987,9,1]],"date-time":"1987-09-01T00:00:00Z","timestamp":557452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[1987,9]]},"abstract":"<jats:p>1. A series of related methylxanthines were studied for their effects on the kinetics of decay of end\u2010plate currents (e.p.c.s) and miniature end\u2010plate currents (m.e.p.c.s) at motor end\u2010plates of the frog. 2. Isobutyl methylxanthine (IBMX, 50 microM\u20103 mM) produced a concentration\u2010dependent depression of the peak e.p.c. and m.e.p.c. amplitude and a change in the kinetics of e.p.c. and m.e.p.c. decay from the normal single\u2010exponential to a double\u2010exponential function. Drug effects of this nature are generally attributed to open\u2010channel blockade. 3. After wash\u2010out of IBMX, the decay of the e.p.c. or m.e.p.c. was restored to a single\u2010exponential function but with a significantly prolonged time constant. 4. Caffeine or theophylline derivatives (0.1\u20104 mM), during exposure to drug, produced effects similar to those observed after the application of IBMX; namely a prolongation of the time course of e.p.c.s and m.e.p.c.s without changing the single\u2010exponential nature of the function. 5. Computer simulations were made of the m.e.p.c.s in IBMX. The effects of IBMX could be fitted to the sequential model of channel block only if the prolonged time constant observed upon wash\u2010out was used for the rate constant of channel closure. Independent calculations of the rate constant of channel closure during IBMX application were in agreement with those measured during wash\u2010out. 6. The theophylline derivative 8\u2010phenyltheophylline, a selective adenosine receptor blocker with minimal effects on phosphodiesterase (PDE), increased the time constant of e.p.c. decay in a manner similar to theophylline and caffeine. Non\u2010xanthine PDE inhibitors, either had no effect on m.e.p.c. decay (papaverine) or decreased the time constant of decay (RO 20\u20101724). It is thus unlikely that PDE inhibition is responsible for the post\u2010junctional effects of IBMX. 7. IBMX (50 microM\u20102 mM) increased quantal ACh release in the virtual absence of extracellular calcium and also increased the efficacy of adenosine derivatives in inhibiting ACh release. Adenosine (10\u2010100 microM) or 2\u2010chloroadenosine (1\u201010 microM) had no effect on the time constant of e.p.c. decay nor did these adenosine receptor agonists alter the post\u2010junctional actions of IBMX. The effects of IBMX on end\u2010plate channel kinetics are thus not due to the blockade of adenosine receptors.(ABSTRACT TRUNCATED AT 400 WORDS)<\/jats:p>","DOI":"10.1113\/jphysiol.1987.sp016684","type":"journal-article","created":{"date-parts":[[2014,12,19]],"date-time":"2014-12-19T06:39:33Z","timestamp":1418971173000},"page":"33-44","source":"Crossref","is-referenced-by-count":7,"title":["Independent control of channel closure and block of open channels by methylxanthines at acetylcholine receptors in frog."],"prefix":"10.1113","volume":"390","author":[{"given":"E M","family":"Silinsky","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S M","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[1987,9]]},"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.1987.sp016684","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.1987.sp016684","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T08:43:17Z","timestamp":1697877797000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.1987.sp016684"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1987,9]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1987,9]]}},"alternative-id":["10.1113\/jphysiol.1987.sp016684"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.1987.sp016684","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[1987,9]]}}}