Effects of PPADS and suramin on contractions and cytoplasmic Ca²⁺ changes evoked by AP₄A, ATP and α,β‐methylene ATP in guinea‐pig urinary bladder

Abstract

1 The contraction and intracellular Ca2+ change evoked by diadenosine tetraphosphate (AP4A) were studied in the outer longitudinal muscle of the guinea-pig urinary bladder and compared with those evoked by ATP and a,fi-methylene ATP (a P2-purinoceptor agonist).2 AP4A, ATP and a,,B-methylene ATP produced concentration-dependent transient contractions. These contractions were inhibited by PPADS (pyridoralphosphate-6-azophenyl-2'-4'-disulphonic acid), 0.3-30 gM, a P2x-purinoceptor antagonist, and suramin, 1-300 gM, a P2-purinoceptor antagonist in a concentration-dependent manner. From Schild plot analysis, the apparent pA2 values for PPADS for contractions evoked by AP4A, ATP and a,#-methylene ATP were 6.86, 6.56, 6.74, and those for suramin were 6.01, 4.59 and 5.12, respectively; the Schild slopes for PPADS were 1.07, 1.14 and 1.06, and, those for suramin 0.75, 1.05 and 1.16, respectively. 3 AP4A (10 gM) and ATP (100 gM) failed to elicit any contraction of the tissue after a desensitization produced by repeated application of c,fl-methylene ATP (1 Mm). 4 In fluorescence experiments with fura-2, the increases in [Ca2+]i and contraction evoked by AP4Awere suppressed by suramin and nifedipine, an L-type Ca21 channel blocker. 5 These findings suggest that P2x-purinoceptors, which are more sensitive to PPADS than suramin, exist on the outer longitudinal muscles of guinea-pig urinary bladder, and that the AP4A-evoked contraction results from Ca2+ influx.

Functional expression of muscarinic and purinoceptors in the urinary bladder of male and female rats and guinea pigs

“…Furthermore, neither suramin nor PPADS (P2-receptor antagonists) reduced the contraction to ATP in rat strips (Kageyama et al, 2000) but both inhibited contraction of guinea pig muscles (Hoyle et al, 1990;Usune et al, 1996). In the present experiments, PPNDS also had a greater effect on guinea pig than rat bladders.…”

Purinergic signalling in the urinary tract in health and disease

“…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].…”

“…It has been proposed that about 20 % of the neurogenic contraction of rat bladder is mediated by purinergic receptors sensitive to ADPβS [284]. The diadenosine polyphosphate, Ap 4 A, contracts the guinea-pig bladder and since this was abolished after desensitisation with α,β-meATP and by suramin, PPADS and nifedipine, it is likely to act through P2X receptors [687].…”

Mesaneni̇n Non-Adrenerji̇k Non-Koli̇nerji̇k Kontrolü : Non-Adrenergic, Non-Cholinergic Control of the Urinary Bladder

“…Atropin ve -metilen ATP varlığında, insan, kobay, sıçan gibi birçok türlerden alınan mesane preparatlarında, postgangliyonik parasempatik sinir stimulasyonuyla oluşturulan kontraktil yanıtlar ortadan kaldırılmaktadır (2,5). Günümüzde, yeni bulunan suramin adlı bir bileşiğin de mesanedeki P 2x purinoseptörlerini antagonize ettiği gösterilmiştir (6). P 2x purinoseptörlerin voltaja bağımlı kalsiyum kanallarını açtığı ortaya konulmuştur.…”