Effects of adenine nucleosides and nucleotides on neuromuscular transmission to the prostatic stroma of the rat

1 The aim of this study was to investigate the effects of adenine nucleosid es and nucleotides on contractility of the smooth muscle of rat prostate gl and. 2 Nerve terminals within rat isolated prostatic tissues were electrically f ield stimulated (60 V, 0.5 ms, 10 Hz, 20 pulses every 60 s). Adenosine 5'-t riphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-monophospha te (AMP) and adenosine had no effect on baseline smooth muscle tone but con centration-dependently inhibited electrically-evoked contractile responses. The relative order of potency was ATP congruent to AMP congruent to adenos ine > ADP. 3 The inhibition by ATP and adenosine of field stimulation-induced contract ions in the rat prostate was antagonized by 8-phenyltheophylline (10 muM), but not by suramin (100 muM) and only slightly by reactive blue 2 (5 muM). 4 The adenosine metabolizing enzyme adenosine deaminase (0.1 unit ml(-1)) i nhibited the inhibitory effects of ATP and adenosine. The P2 purinoceptor a gonist 2-methylthio ATP (10 nM-0.1 mM), had no effect on field stimulation- induced contractions of the rat prostate. 5 ATP and adenosine did not modify the contractile responses of the rat pro state to exogenously added noradrenaline (10 muM). 6 Inhibitory concentration-response curves to a number of adenosine analogu es with differing stabilities and selectivities for the different adenosine receptors yielded a relative rank order of agonist potency of: N-6-cyclope ntyladenosine (CPA) > N-6-cyclohexyladenosine (CHA) congruent to (-)-N-6-(2 -phenylisopropyl)-adenosine (R-PIA) congruent to 5'-(N-ethylcarboxamido)-ad enosine (NECA) > (+)-N-6-(2-phenylisopropyl)-adenosine (S-PIA) > 2-p-[2-car boxyethyl] phenethyl-amino-5'-N-ethylcarboxamido-adenosine (CGS 21680). 7 These results indicate that adenine nucleoside and nucleotide induced inh ibition of electrically-evoked contractions in the rat prostate occurs thro ugh activation of adenosine but not ATP receptors. The relative order of po tency of adenosine analogues is consistent with activation of receptors of the A(1)-adenosine receptor subtype. These receptors appear to be prejuncti onal.