Inhibitory effect of adenosine and adenine nucleotides on potassium-evoked efflux of [3H]-noradrenaline from the rat isolated heart: lack of relationship to prostaglandins.

1 In the isolated heart of the rat prelabelled with [3H]-noradrenaline (NA) and perfused with Krebs solution, administration of potassium (K+ 60 mumol) increased the efflux of total radioactivity and of [3H]-NA in the perfusate. 2 Adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine, but not inosine, dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP) or db cyclic GMP reduced the K+/-evoked overflow of total radioactivity and of intact [3H]-NA, in concentrations too low to cause release of prostaglandins. ATP, ADP and adenosine did not affect tyramine-evoked overflow of tritium. 3 Blockade of prostaglandin synthesis with indomethacin did not alter the inhibitory effect of either ATP, ADP or adenosine on K+/-induced overflow of tritium, thereby indicating that these nucleotides inhibit adrenergic transmission by a mechanism unrelated to stimulation of prostaglandin synthesis. 4 Theophylline which increases entry of calcium (Ca2+) across the cell membrane and reduces its binding in the cell, enhanced K+/-evoked overflow of tritium and diminished the inhibitory effect of ATP, ADP and adenosine on K+/-evoked overflow of tritium from the heart, presumably by interfering with transneuronal Ca2+ metabolism.