RT Journal Article
SR Electronic
T1 Cardiac effects of adenosine and adenosine analogs in guinea-pig atrial and ventricular preparations: evidence against a role of cyclic AMP and cyclic GMP.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 766
OP 774
VO 234
IS 3
A1 R Brückner
A1 A Fenner
A1 W Meyer
A1 T M Nobis
A1 W Schmitz
A1 H Scholz
YR 1985
UL http://jpet.aspetjournals.org/content/234/3/766.abstract
AB The effects of adenosine, the Ri site adenosine receptor agonist (-)-N6-phenylisopropyladenosine (PIA), the Ra site agonist 5'-N-ethylcarboxamideadenosine (NECA) and the P site agonist 2',5'-dideoxyadenosine (DIDA) on force of contraction, cyclic AMP (cAMP) and cyclic GMP (cGMP) content and on transmembrane action potential were studied in isolated electrically driven left auricles and papillary muscles from guinea pigs. Furthermore, the effects on adenylate cyclase activity in a particulate membrane preparation were investigated. In the auricles, adenosine, PIA and NECA had negative inotropic effects which were accompanied by a shortening of the action potential. Theophylline antagonized these effects which are likely mediated by R site adenosine receptors. DIDA was ineffective. Except for a small positive inotropic effect of adenosine the analogs were ineffective in the papillary muscles. None of the mechanical effects was accompanied by a change in cAMP and cGMP content in the intact preparations. In the broken cell preparation PIA and NECA had no effect on adenylate cyclase activity. Adenosine and DIDA inhibited the enzyme. The latter effects can be classified as P site-mediated effects. In conclusion, distinct mechanical, i.e., negative inotropic effects of adenosine and its analogs in the heart are observed in auricular preparations only. These effects are unlikely to be related to the cAMP and/or cGMP system. Instead, they are probably due to a direct shortening of the action potential which, in turn, is conceivably due to an increase in K+ outward current and a secondary decrease in Ca++ inward current. This effect is apparently mediated by cardiac R site adenosine receptors which are not detectably coupled to adenylate cyclase.