1 The pharmacological properties of presynaptic alpha-2-autoreceptors were studied in rat isolated submaxillary glands and atria. Tissue pieces were preincubated with [H-3]-noradrenaline, then superfused with medium containing desipramine, and stimulated electrically. In one series of experiments, pEC30 values of 12-alpha-adrenoceptor antagonists were determined, i.e., negative logarithms of concentrations that increased the electrically evoked overflow of tritium by 30%. In another series, pK(D) values of 9-alpha-adrenoceptor antagonists against the release-inhibiting effect of 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304), and of 3 antagonists against the release-inhibiting effect of methoxamine, were determined. 2 In submaxillary glands, the pEC30 values of the antagonists correlated well with their pK(D) values against UK 14304 (rb = 0.93). The same was true for atria (rb = 0.92). 3 In submaxillary glands, the pK(D) values of 3 antagonists against UK 14304 were very similar to their pK(D) values against methoxamine, with a maximal difference of 0.4. The same was true for atria where the maximal difference was 0.3. 4 The pEC30 values obtained in submaxillary glands correlated significantly with those obtained in atria (rb = 0.81). The same was true for the pK(D) values (rb = 0.79). However, the pEC30 and pK(D) values also indicated consistent differences between the two tissues. 5 It is concluded that the sites of action of the imidazoline UK 14304 (alpha-2-selective), the phenylethylamine noradrenaline, and the phenylethylamine methoxamine alpha-1-selective) are exclusively alpha-2-adrenoceptors. There is no indication for presynaptic alpha-1-adrenoceptors or for an effect of UK 14304 mediated by presynaptic imidazoline receptors. The alpha-2-autoreceptor population in the submaxillary gland differs from that in the atrium. 6 Comparison with studies from the literature indicates that the submaxillary autoreceptors are closely similar to the alpha-2D radioligand binding site found in the bovine pineal gland and probably the rat submaxillary gland. The atrial autoreceptors also conform best to this site, but the agreement is more limited; the atrial autoreceptors may represent a type related to, but distinct from, the alpha-2D site, or a mixture of different types.
