Prazosin has low potency at α_1A‐adrenoceptors and high potency at α_1D‐adrenoceptors in rat vas deferens

Abstract

(1) We have investigated α1 -adrenoceptor subtypes mediating contractions to noradrenaline in epididymal portions of rat vas deferens. (2) Contractions to noradrenaline were investigated in the absence or presence of the noradrenaline transporter blocker cocaine. (3) In the absence of cocaine, contractions to noradrenaline were potently antagonized by RS100329, but not by BMY7378, and so are mediated mainly by α1A -adrenoceptors. (4) In the presence of cocaine, noradrenaline potency was increased, particularly in terms of low concentrations and phasic contractions. Contractions to low concentrations of noradrenaline in the presence of cocaine were resistant to RS100329 but potently antagonized by BMY7378, demonstrating that α1D-adrenoceptors are additionally involved in contractions amplified by cocaine. (5) In the absence of cocaine, prazosin exhibited relatively low potency as an antagonist against the α1A-adrenoceptor-mediated component to the response. In the presence of cocaine, prazosin exhibited higher potency against the α1D-adrenoceptor-mediated component. (6) In conclusion, prazosin has previously unreported selectivity for α1D-over α1A -adrenoceptors in functional studies of rat vas deferens. Contractions of rat vas deferens are mediated by α1A-and α1D -adrenoceptors. The range of prazosin potencies and of receptor subtypes previously reported in rat vas deferens may be explained by the presence of these two subtypes.

Effects of desipramine on prazosin potency at α1A- and α1D-adrenoceptors in rat vas deferens: Implications for the α1L-adrenoceptor subclassification

“…These effects of desipramine are consistent with some selectivity for α 1A -adrenoceptor antagonism since intermittent spikes are mainly α 1D -adrenoceptor mediated (see Cleary et al, 2004;Docherty, 2013). (Fig.…”

“…One obvious difference between studies is the choice of noradrenaline transporter inhibitor: cocaine or desipramine (or none). We have previously reported that cocaine increases prazosin potency in rat vas deferens by increasing the α 1D -adrenoceptor mediated component to the contraction (9.01: Docherty, 2013). In addition, prazosin potency was lowest in studies carried out in the presence of desipramine (8.32-8.35: Ohmura et al, 1992).…”

“…It has been variously suggested that contractions of rat vas deferens to exogenous noradrenaline or adrenaline are mediated predominantly by α 1A -adrenoceptors (Han et al, 1987;Hanft and Gross, 1989;Aboud et al, 1993;Teng et al, 1994;Burt et al, 1995;Buckner et al, 1996;Honner and Docherty, 1999), α 1D -in addition to α 1A -adrenoceptors (Cleary et al, 2004;Docherty, 2012Docherty, , 2013, α 1L -adrenoceptors (Ohmura et al, 1992), or α 1L -in addition to α 1A -adrenoceptors (Buccioni et al, 2009). Prazosin pA 2 values have been reported in a number of studies of rat vas deferens: 8.32-8.39 (Ohmura et al, 1992); 8.59-9.34 (Honner and Docherty,1999); 9.20 (Burt et al, 1995); 9.26 (Aboud et al, 1993); 9.30 (Amobi et al, 1999); 9.35 (Lima et al, 2005).…”

The Adrenergic System in Vascular Smooth Muscle

“…However, receptors reported to be α 1L -adrenoceptors can be demonstrated under slightly altered conditions to be α 1A -adrenoceptors. Hence, in the view of this author, it is likely that the α 1L -adrenoceptor is simply the native α 1A -adrenoceptor, at which prazosin shows low potency functionally [37].…”

“…α 1D -Adrenoceptors are involved in neurotransmission in the pithed rat [35] and in non-vascular tissues such as rat vas deferens [37].…”