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

Abstract

1. The aim of this study was to investigate the effects of adenine nucleosides and nucleotides on contractility of the smooth muscle of rat prostate gland. 2. Nerve terminals within rat isolated prostatic tissues were electrically field stimulated (60 V, 0.5 ms, 10 Hz, 20 pulses every 60 s). Adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP) and adenosine had no effect on baseline smooth muscle tone but concentration-dependently inhibited electrically-evoked contractile responses. The relative order of potency was ATP ≃ AMP ≃ adenosine > ADP. 3. The inhibition by ATP and adenosine of field stimulation-induced contractions in the rat prostate was antagonized by 8-phenyltheophylline (10 μM), but not by suramin (100 μM) and only slightly by reactive blue 2 (5 μM). 4. The adenosine metabolizing enzyme adenosine deaminase (0.1 unit ml-1) inhibited the inhibitory effects of ATP and adenosine. The P2 purinoceptor agonist 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 prostate to exogenously added noradrenaline (10 μM). 6. Inhibitory concentration-response curves to a number of adenosine analogues with differing stabilities and selectivities for the different adenosine receptors yielded a relative rank order of agonist potency of: N6-cyclopentyladenosine (CPA) > N6-cyclohexyladenosine (CHA) ≃ (-)-N6-(2-phenylisopropyl)-adenosine (R-PIA) ≃ 5'-(N-ethylcarboxamido)-adenosine (NECA) > (+)-N6-(2-phenylisopropyl)-adenosine (S-PIA) > 2-p-[2-carboxyethyl]phenethyl-amino-5'-N-ethylcarboxamido-adenosine (CGS 21680). 7. These results indicate that adenine nucleoside and nucleotide induced inhibition of electrically-evoked contractions in the rat prostate occurs through activation of adenosine but not ATP receptors. The relative order of potency of adenosine analogues is consistent with activation of receptors of the A1-adenosine receptor subtype. These receptors appear to be prejunctional.