Adenosine‐ and α,β‐methylene ATP‐induced differential inhibition of cholinergic and non‐cholinergic neurogenic responses in rat urinary bladder

Abstract

1 The effects of adenosine and a,4-methylene adenosine triphosphate (a,4-Me ATP) on single pulseinduced 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; 80V) evoked a biphasic contractile response (abolished by tetrodotoxin, 0.5 x 1O-7M) consisting of a fast (time to peak: 1.02 + 0.07 s) and a slow component 4 Adenosine (10-8M to 1O-4M) caused dose-related differential inhibition of the fast (IC5o, 1.04 + 0.25 x 10-SM) and slow (IC50, 2.18 + 0.69 x 10-6M) components, thereby further supporting two modes of neurotransmission in bladder. 5 Theophylline (10-4M) 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 (10-4M)-and ACh (10-8M)-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 (10-6M) and dipyridamole (10-6M) suggests that endogenous adenosine plays little part in modulation of single pulseinduced 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.

A2B adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission

“…In the present study, EFS and exogenous ATP evoked contractions of the intravesical ureteral strips, which were potentiated as a consequence of the blockade of adenosine receptors with 8-PT. These results suggest that adenosine could exert a physiological tonic in¯uence on the ureteral NANC transmission and would thus be consistent with those obtained in the mouse (Acevedo et al, 1992) and rat (Parija et al, 1991) urinary bladder. The fact that 8-PT increased the contractions induced by two non purinergic agonists (ACh and 5-HT) could indicate that adenosine formed from ATP, either released from nerves or exogenously added, would be diminishing the contractions of the tissue nonspeci®cally.…”

Identification of Atropine- and P2X1Receptor Antagonist-Resistant, Neurogenic Contractions of the Urinary Bladder

“…Similar antagonist-insensitive responses to ATP are also seen in the rat (Bolego et al, 1995;Benkó et al, 2003). In contrast, the response to ATP was abolished by prolonged exposure to ␣,␤-meATP, as reported previously in the guinea pig (Kasakov and Burnstock, 1983), human (Hoyle et al, 1989), rat (Parija et al, 1991), and rabbit (Chancellor et al, 1992) (but see Chen et al, 1992). Why the P2X 1 antagonist-resistant component is sensitive to inhibition by the P2X 1 agonist ␣,␤-meATP is unclear.…”

The effect of in vivo oestrogen pretreatment on the contractile response of rat isolated detrusor muscle

“…Conversely neostigmine (Brading & Mostwin, 1989) and physostigmine potentiated electrical field stimulation at low although less than at high frequencies. There is now good evidence that the non-cholinergic transmitter is adenosine 5'-triphosphate (ATP) (Brading & Mostwin, 1989;Brading & Williams, 1990;Parija et al, 1991), but whether pretreatment affects this mechanism is unknown at present.…”