1 The effects of adenosine receptor agonists upon both electrically-evoked and phenylephrine-induced contractile responses were investigated in the bisected vas deferens and the cauda epididymis of the guinea-pig. Electrical held-stimulation (10 s trains of pulses at 9 Hz, 0.1 ms duration, supramaximal voltage) elicited biphasic and monophasic contractile responses from preparations of bisected vas deferens and cauda epididymis, respectively; these responses were abolished by tetrodotoxin (300 nM). 2 In the prostatic half of the vas deferens the A(1) selective adenosine receptor agonists, N-6-cyclopentyladenosine (CPA) and (2S)-N-6-[2-endo-norbornyl]adenosine ((S)-ENBA) and the non-selective A(1)/A(2) adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA) inhibited electrically-evoked contractions (pIC(50) +/- s.e.mean values 6.15 +/- 0.24, 5.99 +/- 0.26 and 5.51 f0.24, respectively). The responses to CPA were blocked by the Al adenosine receptor antagonist, 8-cyclopentyl-l,3-dipropylxanthine, DPCPX (100 nM). 3 In the epididymal half of the vas deferens NECA potentiated (at less than or equal to 100 nM) and inhibited (at greater than or equal to 1 pM) electrically-evoked contractions. In the presence of the non-selective alpha-adrenoceptor antagonist phentolamine (3 mu M), the alpha(1)-adrenoceptor antagonist, prazosin (100 nM), or at a reduced train length (3s) NECA inhibited electrically-evoked contractions (pIC(50) values 6.05+/-0.25, 5.97+/-0.29 and 5.71+/-0.27, respectively). CPA (at 10 mu M) also inhibited electrically-evoked contractions in this half of the vas deferens. In the presence of prazosin (100 nM), CPA also inhibited electrically-evoked contractions (pIC(50) 6.14+/-0.67); this effect was antagonized by DPCPX (30 nM, apparent pK(B) 8.26+/-0.88). In the presence of the P2 purinoceptor antagonist, suramin (300 mu M), CPA (up to 1 mu M) potentiated electrically-evoked contractions. 4 NECA, CPA and APNEA potentiated electrically-evoked contractions in preparations of cauda epididymis (pEC(50) values 7.49 +/- 0.62, 7.65 +/- 0.74 and 5.84+/-0.86, respectively), the response to CPA was competitively antagonized by DPCPX (100 nM) with an apparent pK(B) value of 7.64+/-0.64. 5 The al-adrenoceptor agonist phenylephrine elicited concentration-dependent contractile responses from preparations of bisected vas deferens and cauda epididymis. NECA (1 mu M) potentiated responses to phenylephrine (less than or equal to 1 mu M) in the epididymal, but not in the prostatic half of the vas deferens. In preparations of epididymis NECA (1 mu M) shifted phenylephrine concentration response curves to the left (4.6 fold). In the presence of a fixed concentration of phenylephrine (1 mu M), NECA elicited concentration-dependent contractions of preparations of the epididymal half of the vas deferens and of the epididymis (pEC(50) values 7.57+/-0.54 and 8.08+/-0.18, respectively). NECA did not potentiate responses to ATP in either the epididymal half of the vas deferens or the epididymis. 6 These studies are consistent with the action of stable adenosine analogues at prejunctional Al and postjunctional Al-like adenosine receptors. The prejunctional Al adenosine receptors only inhibit the electrically-evoked contractions of purinergic origin (an effect predominant in the prostatic half of the vas deferens). At the epididymis, where electrically-evoked contractions are entirely adrenergic, the predominant adenosine receptor agonist effect is a potentiation of alpha(1)-adrenoceptor-, but not of ATP-induced contractility.
