Identification of a single α1‐adrenoceptor corresponding to the α1A‐subtype in rat submaxillary gland

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Abstract
1 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. 2 In saturation studies, [3H]-prazosin bound with high affinity (Kd = 30–39 pM) to a single population of sites in all three preparations. 3 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 α1A- and α1B-adrenoceptor subtypes as described by Morrow & Creese (1986) and Han et al. (1987). 4 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 α1A-adrenoceptors. Rat liver α1-adrenoceptors possessed lower affinity for these ligands (6–65 fold) suggesting that these receptors were of the α1B-subtype. 5 Spiperone exhibited 12.9 fold higher affinity for rat liver α1B-adrenoceptors than for rat submaxillary gland α1A-adrenoceptor and may therefore represent the first α1B-adrenoceptor selective ligand.