α1D–Adrenoceptor Mediated Components to Nerve‐Evoked Contractions in Mouse Vas Deferens

Abstract

Contractions of the mouse vas deferens are mediated by α1‐adrenoceptors and P2X1‐purinoceptors (Brown et al., 1983). α1D‐Adrenoceptors are involved in the nerve‐evoked contraction to a single stimulus (Bexis et al., 2008). In this study, the role of these receptors in contractions to low and high frequency nerve stimulation have been investigated. Whole vas deferens from C57 mice were set up between electrodes in organ baths under 0.5 g tension in Krebs‐Henseleit solution, and stimulated electrically with 10 pulses at 1Hz or 40 pulses at 10 Hz using a Grass stimulator. The response to 1Hz stimulation consisted of discrete peaks of response corresponding to each stimulus. Threshold concentrations of the α1A‐adrenoceptor antagonist RS100329 (1nM) and the α1D‐adrenoceptor antagonist BMY7378 (100nM) significantly reduced contractions to the first pulse, and the non‐selective antagonist prazosin (10 nM) significantly reduced contractions to the first 4 pulses, at 1 Hz, but the combination of prazosin and the purinoceptor antagonist suramin produced marked inhibition of the response to all 10 pulses. The response to 10 Hz stimulation consisted of an early peak and later plateau of contraction. BMY7378 (100 nM) did not significantly affect the 10 Hz response but prazosin (10 nM) and RS100329 (1 nM) significantly reduced contractions, particularly the peak response, and higher concentrations markedly reduced responses. In the presence of the L‐type calcium channel blocker nifedipine, contractions to 10Hz stimulation were markedly reduced, particularly the later plateau component. In the presence of nifedipine, the peak response to 10 Hz stimulation was significantly reduced by prazosin (1nM) and by BMY7378 (100nM), demonstrating a small α1D‐adrenoceptor mediated component. In summary, contractions to 1 Hz stimulation have early α1A‐ and α1D‐adrenoceptor mediated components, but later responses are predominantly purinergic. Contractions even to 10 Hz stimulation have an early small α1D‐adrenoceptor component to the peak response, but both peak and plateau contractions largely involve α1A‐adrenoceptors and purinoceptors. The α1A‐adrenoceptor and purinoceptor components largely involve calcium entry through L‐type channels, but the α1D‐adrenoceptor mediated component involves T‐type calcium channels (Seto et al., 2010). In conclusion, the α1D‐adrenoceptor mediated component to both low and high frequency stimulation is very short‐lived, occuring in the first second of stimulation at low and high frequencies.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.