Subclassification of the presynaptic α 2 ‐autoreceptors in rabbit brain cortex

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1 The pharmacological properties of presynaptic M2-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 x-adrenoceptor antagonists were determined, i.e., negative logarithms of concentrations that increased the electrically evoked overflow of tritium by 30%. In another series, pKD values of 9 aadrenoceptor 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 pKD values against UK 14304 (r = 0.93). The same was true for atria (r = 0.92).3 In submaxillary glands, the pKD values of 3 antagonists against UK14304 were very similar to their pKD 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 pKD values (r = 0.79). However, the pEC30 and pKD values also indicated consistent differences between the two tissues. 5 It is concluded that the sites of action of the imidazoline UK 14304 (x2-selective), the phenylethylamine noradrenaline, and the phenylethylamine methoxamine (a,-selective) are exclusively a2-adrenoceptors. There is no indication for presynaptic a,-adrenoceptors or for an effect of UK 14304 mediated by presynaptic imidazoline receptors. The 02-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 a2D 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 a2D site, or a mixture of different types.

Section: Introductioncontrasting

confidence: 71%

“…The difference may be due to the occurrence of predominantly a2A-autoreceptors in rabbits (Limberger et al, 1991) and &2D-autoreceptors in rats.…”

Section: Properties Of the A2-autoreceptorsmentioning

confidence: 92%

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

Limberger

Trendelenburg

Starke

1992

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“…M2A-Adrenoceptors are reported to be present prejunctionally in the rat vas deferens (Connaughton & Docherty, 1990), rat submandibular gland , and rabbit brain cortex (Limberger et al, 1991). The low potency of prazosin prejunctionally at the cholinergic nerves of guinea-pig ileum (Kaposci et al, 1987), at the noradrenergic and 5-hydroxytryptaminergic nerves of rat brain synaptosomes (Gobbi et al, 1991), and at antagonizing actions of endogenous noradrenaline in rat cerebral cortex (Harsing & Vizi, 1991), may suggest that these receptors are also x2A.…”

Section: Discussionmentioning

confidence: 99%

Investigations of the subtype of α₂‐adrenoceptor mediating contractions of the human saphenous vein

Smith

Connaughton

Docherty

1992

We have examined the effects of a series of α2‐adrenoceptor antagonists against isometric contractions to noradrenaline in human saphenous vein, and correlated these potencies with affinities for the α2A‐ligand binding site of human platelet and the α2B‐ligand binding site of rat kidney. The α2B‐selective adrenoceptor antagonists, prazosin, ARC 239 and HV 723 showed high, and the α2A‐selective antagonist BRL 44408 showed low, potency in human saphenous vein. Potency in human saphenous vein correlated better with affinity for the α2B‐ligand binding site (r =0.71, n = 12, P < 0.01) than with affinity for the α2A‐ligand binding site (r = 0.56, n = 12, non significant). It is concluded that the postjunctional α2‐adenoceptor of human saphenous vein resembles an α2B‐ligand binding site more than an α2A‐ligand binding site.

“…synaptic a2-autoreceptors were compared in rat heart and vas deferens (Doxey & Everitt, 1977). In rabbit brain cortex, pulmonary artery, kidney and atria the a2-autoreceptors have been characterized as a2A (Limberger et al, 1991;1995a;Molderings & G6thert, 1992;Trendelenburg et al, 1993). Based on these results, it has been proposed that 'the majority of a2-autoreceptors generally are a2D in the rat and a2A in the rabbit.…”

mentioning

confidence: 99%

α_2c‐Adrenoceptor‐modulated release of noradrenaline in human right atrium

Rump

Böhmann

Schaible

et al. 1995

1 The aim of the present study was to characterize the presynaptic a2-autoreceptors in human right atrium in terms of the a2AD system. Segments of atrial appendages were preincubated with [3H]-noradrenaline and then superfused in the presence of cocaine and stimulated electrically. pEC30% values of eight a-adrenoceptor antagonists with discriminatory power were determined. pEC30% is the negative logarithm of the antagonist concentration that increased the stimulation-induced overflow of tritium by 30%. For four antagonists, the dissociation constant KD was determined, in addition to pEC30%, against the overflow-inhibiting effect of 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) under autoinhibition-free conditions. 2 pEC30% and KD values yielded identical rank orders of antagonist affinity (rauwolscine > WB 4101> phentolamine > prazosin) suggesting that both released noradrenaline and the exogenous agonist UK 14,304 activated the same receptor to inhibit release. In conclusion, the presynaptic a2-autoreceptors in human right atrium are X2C. In this they agree with the previously characterized a2-autoreceptors in human kidney. The a2C classification possibly separates, in general, human a2-autoreceptors from those in lagomorph (rabbit) and rodent (rat, mouse, guinea pig) species that have been proposed to be predominantly a2A or a2D.