Identification of a single alpha 1-adrenoceptor corresponding to the alpha 1A-subtype in rat submaxillary gland.
1. The alpha 1-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 alpha 1-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 alpha 1A- and alpha 1B-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 alpha 1-adrenoceptors. However, there were pharmacological differences between the receptors in these two preparations. Rat submaxillary gland alpha 1-adrenoceptors displayed high affinity for amidephrine, benoxathian, oxymetazoline, phentolamine and WB 4101 and therefore appeared to represent alpha 1A-adrenoceptors. Rat liver alpha 1-adrenoceptors possessed lower affinity for these ligands (6-65 fold) suggesting that these receptors were of the alpha 1B-subtype. 5. Spiperone exhibited 12.9 fold higher affinity for rat liver alpha 1B-adrenoceptors than for rat submaxillary gland alpha 1A-adrenoceptor and may therefore represent the first alpha 1B-adrenoceptor selective ligand.
Michel
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Institute of Pharmacology, Syntex Research, Palo Alto, CA 94303.
Loury
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Whiting
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D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D013363:Submandibular Gland / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha