Effect of diadenosine polyphosphates on catecholamine secretion from isolated chromaffin cells

1. The action of several diadenosine polyphosphates (AP3A, AP4A and AP5A) on basal, and on nicotine- and high K(+)-evoked, catecholamine (CA) release has been investigated. Each of the three diadenosine polyphosphates weakly but significantly increased basal CA secretion. This enhancement represented about 10% of the response evoked by 2 microM nicotine. 2. The evoked secretory response to diadenosine polyphosphates had an absolute requirement for extracellular Ca2+. 3. In contrast, these compounds had an inhibitory action on nicotine-evoked release. This response was concentration-dependent, EC50 values being 3.2 +/- 0.4 microM, 4.0 +/- 1.6 microM and 19.3 +/- 4.0 microM for AP3A, AP4A, and AP5A, respectively. The lower the concentration of nicotine used to evoke secretion, the higher the inhibitory power of these compounds. 4. The CA secretion evoked by K(+)-rich solutions was further enhanced by AP3A and AP5A, whereas AP4A inhibited it. The possible physiological role of these dual actions is discussed.