Contribution of P₂‐purinoceptors to neurogenic contraction of rat urinary bladder smooth muscle

Abstract

The contribution of P2‐purinoceptors to neurogenic contraction was investigated in rat urinary bladder smooth muscle by measurement of isotonic tension. Contraction of rat urinary bladder smooth muscle induced by electrical stimulation was decreased to 84.19±3.90% of the control (n= 16) in the presence of atropine (1 μm), which was further decreased to 38.80 ±2.75% of the control (n = 49) in the presence of both atropine and 10 μm α,β‐methylene adenosine 5′‐triphosphate (α,β‐Me ATP). The contractile response induced by electrical stimulation in the presence of atropine and α,β‐Me ATP was decreased to 27.81 ±4.07% (n = 23) and 26.63 ±5.01% (n = 15) of the control, by the addition of 100 μm cibacron blue 3GA and 100 μm suramin, respectively. The application of 100 μm adenosine 5′‐0–2‐thiodiphosphate (ADPβS) in the presence of atropine and α,β‐Me ATP decreased the contractile response induced by electrical stimulations to 17.15 ±3.71% (n=15) of the control. Pretreatment of muscle strips with 100 μm ADPβS significantly reduced the response to either 200 μm α,β‐methylene adenosine 5′‐diphosphate or 200 μm ADPβS. Uridine 5′‐triphosphate (100 μm to 1 mM) concentration‐dependently contracted muscle strips, and this contraction was significantly antagonized by desensitization of P2‐receptors with α,β‐Me ATP (10 μm), and completely antagonized by pretreatment of muscle strips with both α,β‐Me ATP and ADPβS (100 μm). Di(adenosine‐5′) tetraphosphate (30 and 100 μm) contracted muscle strips, whereas it failed to contract after desensitization of P2‐receptors. It is suggested that about 20% of the neurogenic contraction of rat urinary bladder smooth muscle is mediated via ADPβS‐sensitive purinoceptors.

Alterations in neurogenically mediated contractile responses of urinary bladder in rats with diabetes

“…␣,␤-MeATP, an ATP analog, is resistant to ATPase and selectively acts on the P2X receptor. Thus P2X receptors can be desensitized through repeated application of ␣,␤-MeATP (15). Additionally, there is always a small residual NANC component of detrusor contraction that is not mediated by either M or P2X receptors (22,56).…”

“…One possible mechanism is that ATP may act on another type of P2 receptor, but not on the P2X receptor (15). Although multiple P2X receptors have been identified in mice and human bladders, it is generally believed that P2X1 receptors are the predominant subtype involved in the neurally evoked purinergic excitatory effects (39,50).…”

Activation and Regulation of Purinergic P2X Receptor Channels

“…Here we use term RB-2 to describe the antagonistic actions of the mixture of terminal ring meta-and para-sulfonate, and we discuss separately the allosteric actions of Cibacron blue 3GA, the purified ortho isomer, at recombinant P2XRs. The antagonistic actions of RB-2 were observed in several diverse ATPmediated physiological responses, such as rat urinary bladder smooth muscle contraction (Hashimoto and Kokubun, 1995), rat cecum inhibitory junction potentials (Manzini et al, 1986), and calcium influx in rat parotid acinar cells (Soltoff et al, 1989). It has also been suggested that RB-2 inhibits ectonucleotidase activity in X. laevis oocytes and ATP-induced inflammation of the mouse hind paw .…”

The effect of hypercholesterolemia on the contractions of detrusor strips in response to neural stimulation in rats

“…When cholinergic and purinergic components of EFSinduced contractile responses of detrusor smooth muscles were abolished, there remained a considerable amount of contraction (33% in NC group, 35% in HC group). Incomplete desensitization of P2X purinoceptors or the presence of other purinoceptors in the rat detrusor smooth muscle (24,33) could be involved in the residual contractile component together with the other NANC transmitter(s) released (18,(34)(35)(36).…”