ADENOSINE-METHYLENE AND ALPHA,BETA-METHYLENE ATP-INDUCED DIFFERENTIAL INHIBITION OF CHOLINERGIC AND NONCHOLINERGIC NEUROGENIC RESPONSES IN RAT URINARY-BLADDER

1 The effects of adenosine and alpha,beta-methylene adenosine triphosphate (alpha,beta-Me ATP) on single pulse-induced neurogenic responses and contractions caused by exogenously applied acetylcholine (ACh) and adenosine triphosphate (ATP) were examined in rat urinary bladder. 2 Application of single pulse stimulation (1 ms; 80 V) evoked a biphasic contractile response (abolished by tetrodotoxin, 0.5 x 10(-7)M) consisting of a fast (time to peak: 1.02 +/- 0.07s) and a slow component (time to peak: 4.92 +/- 1.6s). The selective inhibition of the slow component by atropine (3 x 10(-6)M) suggests the participation of both cholinergic and non-cholinergic neurotransmitters. 3 alpha,beta-Me ATP (5 x 10(-6)M) abolished ATP (10(-4)M)-induced contractions without altering those to ACh (10(-6)M). Further, the selective inhibition of the fast component of the neurogenic response by alpha,beta-Me ATP is suggestive of the contribution of endogenous ATP to the non-chlinergic component. 4 Adenosine (10(-8)M to 10(-4)M) caused dose-related differential inhibition of the fast (IC50, 1.04 +/- 0.25 x 10(-5)M) and slow (IC50, 2.18 +/- 0.69 x 10(-6)M) components, thereby further supporting two modes of neurotransmission in bladder. 5 Theophylline (10(-4)M) antagonized the inhibitory effects of adenosine on the non-cholinergic component, thereby implicating the participation of P1-purinoceptors in neuromodulation. In contrast, theophylline at this concentration enhanced the adenosine-induced inhibition of the cholinergic component. 6 The magnitude of ATP (10(-4)M)- and ACh (10(-8)M)-induced contractions were almost identical to those of the fast and slow components of the neurogenic response, respectively. Comparable reduction of ATP (30.2 +/- 3.4%) and ACh (100%) contractions to those of fast (44.2 +/- 6.5%) and slow (88.2 +/- 5.5%) components suggests the involvement of a postjunctional mechanism in adenosine-induced differential inhibition of neurogenic responses. 7 The lack of effect of erythro-6-amino-9-(2-hydroxy-3-nonyl) adenosine hydrochloride (10(-6)M) and dipyridamole (10(-6)M) suggests that endogenous adenosine plays little part in modulation of single pulse-induced neurogenic response. 8 The results of the present study suggest that fast and slow components of neurogenic response are mediated through ATP and ACh, respectively, possibly co-released from the same neurone in the rat bladder.