The fate of isoprenaline after inhibition of O-methylation and of extraneuronal uptake.

In order to study the fate of isoprenaline in the presence of drugs which inhibit its extraneuronal uptake and O-methylation, strips of canine lateral saphenous veins strips were incubated for 60 min with 3H-isoprenaline (2 microM) in the presence of cortexone 60 microM and U-0521 100 microM. Cortexone reduced to about 50% the amount of 3H-isoprenaline accumulated in the presence of U-0521 and the addition of cocaine further reduced it by about 30%. Field stimulation of strips treated with cortexone and U-0521 resulted in the release of significant, although small, amounts of 3H-isoprenaline; this release was prevented by cocaine or by pretreatment with reserpine. Thus, when extraneuronal uptake and O-methylation are inhibited, isoprenaline behaves like a false transmitter. Even in the presence of cortexone, U-0521 and cocaine, a considerable amount of isoprenaline accumulates in the strips, presumably in non-muscular structures of the tunica media.