Evidence of Adenosine 5′-Triphosphate Release From Nerve and P2x-Purinoceptor Mediated Contraction During Electrical Stimulation of Rat Urinary Bladder Smooth Muscle

Abstract

The results of the present study give evidence to support purinergic nerve-mediated bladder smooth muscle contractions in the rat. Among the purine nucleotides, ATP is the dominant purinergic neurotransmitter released and P2x receptor activation is responsible for the NANC contractile response.

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

“…PPADS at 30 M (Ziganshin et al, 2002) and 100 M suramin (Hoyle et al, 1990) inhibited contractions in the guinea pig evoked at 4 Hz EFS by 30 -40%. Similar effects were seen in rabbit (Ziganshin et al, 1993;Creed et al, 1994), rat (Tong et al, 1997;Hedge et al, 1998;Benkó et al, 2003;Knight and Burnstock, 2004), and sheep (Creed et al, 1994). The photolysable, irreversible P2X antagonist ANAPP 3 (arylazido aminopropionyl ATP) also depressed contractions elicited by 4 Hz EFS in guinea pig by approximately only half (Westfall et al, 1983).…”

Purinergic signalling in the urinary tract in health and disease

“…After suramin was shown to be a reversible P2 purinergic receptor antagonist in the mouse vas deferens [217], it was reported to reduce the responses to both purinergic agonists and the NANC component of neural responses in the guineapig, rat and shrew bladders [312,314,680]. In a study of the effects of suramin on the responses to nerve stimulation and ATP in the bladder muscle strips from guinea-pigs, rabbits, monkeys and sheep and detrusor strips from humans, it was show that it produced parallel inhibition in guinea-pig and rabbit, but in sheep and human tissue, where the purinergic nerve component was smaller, the effect of suramin was difficult to assess because of increase in spontaneous activity [166].…”

“…Pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS) was introduced as a P2X antagonist in the vas deferens in 1992 [405] and later was also shown to be effective in selectively antagonising P2X purinoceptor-mediated contractions in the rabbit urinary bladder produced by exogenous α,β-meATP and by purinergic nerve stimulation [680,763]. P2X receptors in the guinea-pig bladder were shown to be more sensitive to PPADS than suramin, and diadenosine tetraphosphate (Ap 4 A) appeared to be acting through this P2X receptor since, like ATP responses, responses to Ap 4 A were abolished alter desensitisation with α,β-meATP [687].…”

“…In the mini-pig bladder it appears that the neurally evoked relaxation which follows the initial cholinergic contraction of the bladder neck is mediated by P2Y receptors [680]. In another study of pig bladder neck, it was shown that ATP after breakdown to ADP caused relaxation via P2Y 1 receptors and, after breakdown to adenosine, relaxation via A 2A receptors [294].…”

Enhanced production of nitric oxide may contribute to the induction of detrusor underactivity in sucrose fed rats

“…On the other hand, elevated expression levels for muscarinic receptors have been observed during bladder hypertrophic conditions [19]; consequently, enhanced cholinergic receptor activation during EFS may be anticipated. Similarly, increased release of ATP from nerve sources during EFS [20] could facilitate stronger detrusor contractions in association with the increased muscle mass and action on other purinergic receptors not involved in NO production (see below). In the normal rat bladder, the post-junctional release of ATP produces a transient activation of P2X1 receptors on smooth muscle cells that can generate contractions of a considerable magnitude, which are also increased during pathological bladder conditions [21,22].…”