Pharmacological characterization of presynaptic α2-autoreceptors in rat submaxillary gland and heart atrium

Abstract

1 The pharmacological properties of presynaptic α₂-autoreceptors were studied in rat isolated submaxillary glands and atria. Tissue pieces were preincubated with [³H]-noradrenaline, then superfused with medium containing desipramine, and stimulated electrically. In one series of experiments, pEC₃₀ values of 12 α-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 α-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 (r = 0.93). The same was true for atria (r = 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 (r = 0.81). The same was true for the pK_D values (r = 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 (α₂-selective), the phenylethylamine noradrenaline, and the phenylethylamine methoxamine (α₁-selective) are exclusively α₂-adrenoceptors. There is no indication for presynaptic α₁-adrenoceptors or for an effect of UK 14304 mediated by presynaptic imidazoline receptors. The α₂-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 α_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 α_2D site, or a mixture of different types.