Facilitatory and inhibitory modulation by endogenous adenosine of noradrenaline release in the epididymal portion of rat vas deferens

Summary

The present study aimed at determining the modulation by adenosine of the release of noradrenaline in the epididymal portion of the rat vas deferens. The tissues were treated with pargyline and perifused in the presence of desipramine and yohimbine. Up to four periods of electrical stimulation were applied (5 Hz, 9 min).

The A₁-adenosine receptor selective agonist R-N⁶-phenylisopropyladenosine (R-PIA; 100–900 nmol·l⁻¹) reduced, whereas the A_2A-receptor selective agonist 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine (CGS21680; 3–30nmol·l⁻¹) increased the electrically-evoked noradrenaline overflow in a concentration-dependent manner. The nonselective agonist 5′-N-ethy1carboxamidoadenosine (NECA; 30–300 nmol·l⁻¹) reduced noradrenaline overflow, but the effect did not depend on the concentration. Adenosine deaminase at the concentration of 0.5 μ·ml⁻¹ decreased but at that of 2.0 μ·ml⁻¹ increased noradrenaline overflow. The inhibitors of adenosine uptake, S-(4-nitrobenzyl)-6-thioinosine (NBTI; 50 nmol·l⁻¹) and dipyridamole (3 μmol·l⁻¹), increased the electrically-evoked noradrenaline overflow. The A₁-adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 20 nmol·l⁻¹) caused an increase whereas the A₂-adenosine receptor antagonist 3,7-dimethyl-1-(2-propynyl)xanthine (DMPX; 0.1 μmol·l⁻¹) caused a decrease. NBTI (50 nmol·l⁻¹), partially antagonized the effect of both DPCPX (20 nmol·l⁻¹) and DMPX (0.1 μmol·l⁻¹).

It is concluded that, in the epididymal portion of the rat vas deferens, endogenous adenosine tonically modulates the release of noradrenaline evoked by electrical stimulation, through activation of both inhibitory (A₁) and facilitatory (A_2A) adenosine receptors.