Comparison of the effects of beta-phenylethylamine and d-amphetamine on rat isolated atria

beta-Phenylethylamine (PEA) produced a positive chronotropic effect in the spontaneously beating isolated rat atria. The concentration-response curves to PEA and to d-amphetamine (AMPH) were virtually superimposed and potentiated to the same extent by inhibition of monoamine oxidase with pargyline. As reported for AMPH, the rate accelerating effect of PEA was abolished by pretreatment with reserpine. In the reserpinized tissue, the responses to PEA were partly restored by pargyline pretreatment and fully restored after the incubation with norepinephrine (NE). Repeated exposures to high concentrations of both PEA and AMPH produced tachyphylaxis to low concentrations of the amines but did not modify the endogenous atrial content of NE. in atria labeled with [3H]NE, PEA (6.4 microM) and AMPH (7.9 microM) increased the overflow of tritium mainly as unmetabolized [3H] NE (90%). For both drugs the increase in 3H-transmitter outflow coincided with the positive chronotropic response and it was independent on external Ca++. Cocaine (3.3 microM), which inhibits the uptake mechanism of catecholamines, displaced to the right the concentration-response curves to both PEA and AMPH and reduced the overflow of [3H]NE elicited by either amine. The release of 3H-products elicited by PEA was not modified by drugs that inhibit the uptake mechanism of NE accumulation, such as 26 microM corticosterone or 28 microM hydrocortisone. The results presented show that PEA behaves as AMPH as far as the mechanism of their indirect sympathomimetic effect is concerned. If accepted that PEA and AMPH, due to their high lipid solubility, might freely diffuse into nerves, the antagonism caused by cocaine on the effects of both amines could be interpreted as being the result of the inhibition by this drug of the carrier-mediated efflux of NE.