Accession Number : ADA274875


Title :   Effects of Potassium Channel Blockers on the Negative Inotropic Responses Induced by Cromakalim and Pinacidil in Guinea Pig Atrium


Corporate Author : DEFENCE SCIENCE AND TECHNOLOGY ORGANISATION CANBERRA (AUSTRALIA)


Personal Author(s) : Lau, Wai-Man


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a274875.pdf


Report Date : Jan 1992


Pagination or Media Count : 12


Abstract : The K+ channel openers cromakalim and pinacidil induced a concentration-dependent reduction in atrial contraction force with EC50 values of 25 +/- 2 and 37 +/- 2 micromol/l, respectively. This depressant effect was antagonised by 50 micromal/l tacrine which displaced the concentration-response curves of cromakalim and pinacidil to the right. The respective DR50 values were 3.8 and 2.3. Increasing the tacrine concentration (100 and 500 micromol/l) produced no additional effect on the concentration-response relationships. Addition of 1 micromol/l atropine enhanced the antagonism due to tacrine by increasing the DR50 value from 3.8 to 6.5 for cromakalim and from 2.3 to 5.2 for pinacidil. Glibenclamide, an ATP-sensitive K+ channel blocker, competitively inhibited the negative inotropic effects of cromakalim and pinacidil. The respective dissociation constants for glibenclamide against cromakalim and pinacidil were 0.57 and 0.35 Micromol/l. Neither apamin nor variation in external Ca2+ concentration affected the negative inotropic effects of the K+ channel openers. It was suggested that the mechanical effects of cromakalim and pinacidil are mediated through the ATP-sensitive K+ channels in the heart


Descriptors :   *POTASSIUM , REPRINTS , REDUCTION , VARIATIONS , RESPONSE , MUSCLES , CONTRACTION , GUINEA PIGS , ADENOSINE PHOSPHATES , ATROPINE , PHARMACOLOGY , AUSTRALIA , DISSOCIATION , CHANNELS , HEART


Subject Categories : Biochemistry
      Anatomy and Physiology
      Pharmacology
      Organic Chemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE