The α₁‐adrenoceptors present in membranes of rat liver, cortex and submaxillary gland were labelled with [³H]‐prazosin and the affinity of 15 ligands for these receptors was determined. In saturation studies, [³H]‐prazosin bound with high affinity (K_d = 30–39 pM) to a single population of sites in all three preparations. In competition studies using rat cortex, evidence for heterogeneity of the α₁‐adrenoceptor binding sites was obtained. Displacement isotherms for amidephrine, benoxathian, oxymetazoline, phentolamine and WB 4101 were biphasic and were consistent with the presence of both α_1A‐ and α_1B‐adrenoceptor subtypes as described by Morrow & Creese (1986) and Han et al. (1987). The rat liver and submaxillary gland membrane preparations both possessed homogeneous populations of α₁‐adrenoceptors. However, there were pharmacological differences between the receptors in these two preparations. Rat submaxillary gland α₁‐adrenoceptors displayed high affinity for amidephrine, benoxathian, oxymetazoline, phentolamine and WB 4101 and therefore appeared to represent α_1A‐adrenoceptors. Rat liver α₁‐adrenoceptors possessed lower affinity for these ligands (6–65 fold) suggesting that these receptors were of the α_1B‐subtype. Spiperone exhibited 12.9 fold higher affinity for rat liver α_1B‐adrenoceptors than for rat submaxillary gland α_1A‐adrenoceptor and may therefore represent the first α_1B‐adrenoceptor selective ligand.

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