Prejunctional alpha-adrenoreceptors subserve a physiological role in cardiac noradrenergic transmission

1 The question whether prejunctional alpha-adrenoreceptors subserve a physiological role in a noradrenaline-mediated autoinhibitory feedback loop has been studied in guinea-pig isolated atria by stimulating the accelerans nerve and measuring chronotropic responses and the release of radioactivity after labelling transmitter stores with 3H-noradrenaline. 2 Phentolamine (0.3 micrometer) significantly enhanced chronotropic responses when stimulation was with 0.5 Hz for 30 s, but the increase in the release of radioactivity was too small to be measured reliably. When the frequency of stimulation was increased to 4 Hz for 30 s, phentolamine significantly increased the release of radioactivity but the chronotropic response to stimulation was near maximal and phentolamine had no significant effect on it. 3 With prolonged stimulation (12 min) at the lower frequency (0.5 Hz), both the release of radioactivity and the chronotropic response to stimulation were significantly enhanced by phentolamine (3 micrometers). 4 The results support a physiological role for prejunctional alpha-adrenoreceptors in guinea-pig isolated atria.