Evidence that the α1L‐adrenoceptor is the native α1A‐adrenoceptor in rat vas deferens

Abstract

A 4th functional subtype of α1‐adrenoceptor, the α1L‐adrenoceptor, present in rat vas deferens, has been proposed at which prazosin has low potency (Ohmura et al., 1992). The subtypes of α1‐adrenoceptor mediating contractions of rat vas deferens to norepinephrine (NE) have been examined employing α1A‐antagonist RS100329 and α1D‐antagonist BMY7378 and the non‐selective antagonist prazosin. In presence of cocaine (3 μM) to block the NE transporter, NE potency (6.14±0.15, n=34) was significantly increased (P<0.05) as compared to in the absence of cocaine (5.30±0.10, n=21). Cocaine amplified contractions to low concentrations of NE. BMY7378 was more potent against contractions to NE in the presence of cocaine, whereas RS100329 was more potent in absence of cocaine. Prazosin, like BMY7378, was more potent in the presence of cocaine, suggesting α1D‐adrenoceptor selectivity. Prazosin pA2 values were 8.34 (slope ‐ 0.78±0.07) in absence of cocaine and 9.01 (slope −0.93±0.12) in presence of cocaine, with the lower value indicative of α1A‐adrenoceptor potency, and the higher value α1D‐adrenoceptor potency. Hence, it is concluded that the α1L‐adrenoceptor reported in rat vas deferens is not a functional isoform of the α1A‐adrenoceptor, it is the native α1A‐adrenoceptor at which prazosin shows lower potency.